You searched for subject:(Small molecules).
Showing records 1 – 30 of
203 total matches.
◁ [1] [2] [3] [4] [5] [6] [7] ▶
University of Miami
1.
Lopez, Christopher J.
Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses.
Degree: PhD, Chemistry (Arts and Sciences), 2014, University of Miami
URL: https://scholarlyrepository.miami.edu/oa_dissertations/1348 
► Part I. Small organic molecules can play important medicinal roles as markers for antitumor agents, drug delivery, drug discovery, and proteins. However, many small…
(more)
▼ Part I.
Small organic
molecules can play important medicinal roles as markers for antitumor agents, drug delivery, drug discovery, and proteins. However, many
small organic
molecules aggregate, which can significantly alter their functionality. Therefore, understanding the aggregation process in these
molecules is important. In this work, nuclear magnetic resonance (NMR) was used to study the aggregation of Sunset Yellow FCF, an organic dye, and cromolyn sodium, an asthma drug, by measuring changes in chemical shift, longitudinal (T1) and transverse (T2) relaxation times, and self-diffusion coefficients as a function of concentration and solution ionic strength. The NMR studies were also complemented using UV-visible spectroscopy, dynamic light scattering, and viscosity, pH, conductivity measurements. Models for aggregation in these
molecules were refined to best fit all of the experimental data. Part II. In this work, we have developed shaped pulses that are capable of selectively suppressing magnetization with particular values of T1 and T2 relaxation times. These pulses, referred to as relaxation selective pulses, were optimized using gradient ascent pulse engineering (GRAPE) algorithm to be optimal with respect to selectivity while being robust to magnetic field inhomogeneity. When combined with pulsed field gradients, these pulses could be used to selectively suppress the magnetization for
molecules with particular self-diffusion coefficients. Applications of these pulses to spectral editing and solvent suppression were performed.
Advisors/Committee Members: Jamie D. Walls, Françisco M. Raymo, T. K. Harris, Edwin Rivera.
Subjects/Keywords: Aggregation of small organic molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lopez, C. J. (2014). Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/1348
Chicago Manual of Style (16th Edition):
Lopez, Christopher J. “Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses.” 2014. Doctoral Dissertation, University of Miami. Accessed January 20, 2021.
https://scholarlyrepository.miami.edu/oa_dissertations/1348.
MLA Handbook (7th Edition):
Lopez, Christopher J. “Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses.” 2014. Web. 20 Jan 2021.
Vancouver:
Lopez CJ. Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses. [Internet] [Doctoral dissertation]. University of Miami; 2014. [cited 2021 Jan 20].
Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1348.
Council of Science Editors:
Lopez CJ. Part I. NMR Studies of Aggregation in Organic Dyes and Salts Part II. Design of Relaxation and Diffusion Selective Pulses. [Doctoral Dissertation]. University of Miami; 2014. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1348
University of New South Wales
2.
Bonello, Teresa.
Characterising the impact of tropomyosin targeting compounds on the actin cytoskeleton.
Degree: Medical Sciences, 2013, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/52946
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11624/SOURCE01?view=true
► Targeting specific actin filament populations involved in tumour cell function represents a long-standing challenge in the area of anti-cancer drug development. The tropomyosin (Tm) family…
(more)
▼ Targeting specific actin filament populations involved in tumour cell function represents a long-standing challenge in the area of anti-cancer drug development. The tropomyosin (Tm) family of actin-binding proteins, define functionally distinct actin filament populations, and as such represent attractive candidates for drug targeting. As cells transform they become increasingly reliant on a restricted repertoire of Tms, including the isoform Tm5NM1. To test the hypothesis that targeting Tm5NM1 can perturb actin-filament function,
small molecules were developed using computational docking models against the C- and N-terminus of Tm5NM1. A biochemical and cell-based approach was taken to investigate the nature and specificity of the drug-target interaction.
Small molecules were first screened for activity against a panel of neuroblastoma and melanoma cell lines. Several lead compounds were identified that reduced cell viability and disrupted Tm5NM1-containing actin filament bundles in a dose-dependent manner. To delineate a molecular mechanism of action, select compounds were investigated for activity in biochemical assays using recombinant human Tm5NM1. Anti-Tm compound was found to reduce the binding affinity of Tm5NM1 for filamentous actin. This effect was specific to Tm5NM1, with no respective impact on the binding affinity of muscle Tm for actin. The compounds were also found to alter Tm5NM1-regulated actin filament kinetics, resulting in a slower rate of actin polymerisation and enhanced actin filament depolymerisation. To investigate if structural changes were mediating the impact on Tm5NM1 function, N- and C-terminal peptides were employed to model the intermolecular junction between two Tm5NM1 dimers. The conformational stability of the intermolecular junction was unchanged in the presence of anti-Tm compound, which would suggest that these
small molecules perturb Tm5NM1 function by interfering with the weak electrostatic interactions involved in binding actin and not by disrupting core stability. Taken together, the work presented in this thesis describes a novel class of compounds which act to modulate the function of Tm5NM1. Importantly, this data supports targeting distinct Tm isoforms to perturb actin filament function, with significant clinical implications for the treatment of cancer.
Advisors/Committee Members: Gunning, Peter, Faculty of Medicine, UNSW, Stehn, Justine, Faculty of Medicine, UNSW.
Subjects/Keywords: Small molecules; Actin; Tropomyosin; Cancer
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Bonello, T. (2013). Characterising the impact of tropomyosin targeting compounds on the actin cytoskeleton. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52946 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11624/SOURCE01?view=true
Chicago Manual of Style (16th Edition):
Bonello, Teresa. “Characterising the impact of tropomyosin targeting compounds on the actin cytoskeleton.” 2013. Doctoral Dissertation, University of New South Wales. Accessed January 20, 2021.
http://handle.unsw.edu.au/1959.4/52946 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11624/SOURCE01?view=true.
MLA Handbook (7th Edition):
Bonello, Teresa. “Characterising the impact of tropomyosin targeting compounds on the actin cytoskeleton.” 2013. Web. 20 Jan 2021.
Vancouver:
Bonello T. Characterising the impact of tropomyosin targeting compounds on the actin cytoskeleton. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2021 Jan 20].
Available from: http://handle.unsw.edu.au/1959.4/52946 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11624/SOURCE01?view=true.
Council of Science Editors:
Bonello T. Characterising the impact of tropomyosin targeting compounds on the actin cytoskeleton. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/52946 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11624/SOURCE01?view=true
3.
Wijaya, Juwina.
Utilizing Small Molecules to Study Mitochondrial Presequence-Degrading Protease.
Degree: Biochemistry & Molecular Biology, 2015, UCLA
URL: http://www.escholarship.org/uc/item/8nm1z5z8
► Proper mitochondrial function contributes to cell’s health and integrity. Perturbations in mitochondrial homeostasis have been linked to diseases, specifically neurodegenerative diseases. Understanding the players of…
(more)
▼ Proper mitochondrial function contributes to cell’s health and integrity. Perturbations in mitochondrial homeostasis have been linked to diseases, specifically neurodegenerative diseases. Understanding the players of mitochondrial homeostasis will be beneficial for identification of potential therapeutic pathways. The mitochondrion is equipped with proteases that together serve as a quality control system to maintain homeostasis. While knockout using yeast genetics and RNAi approaches are powerful, new tools that are more rapid and specific are needed to elucidate the role of mitochondrial proteases. In this study, I utilize a high-throughput screening approach to discover and utilize small molecule modulators to characterize presequence-degrading protease (PreP). PreP degrades N-terminal mitochondrial-targeting sequences and other small bioactive peptides, including amyloid-beta peptide, implicating it in Alzheimer’s Diseases. Nonetheless, not much is known about this protease. An in vitro fluorescence donor-quencher based assay was adapted for high-throughput screening of PreP modulators. From a collection of over 100,000 drug-like small molecules, we discovered numerous modulators of PreP. MitoBloCK-60 was identified as a specific inhibitor of PreP. This piperazine-derivative does not uncouple mitochondria and affect viability of cells. Crystal structure of small molecule-bound protein at 2.3 Å revealed key bindings and specificity determinants. MitoBloCK-60 binds within the catalytic chamber of PreP, specifically at the substrate recognition exosite, inducing a conformational change in PreP that limits substrate binding. MitoBloCK-60 treatment in cultured cells suggests the role of PreP in mitochondrial quality control pathways. By being able to modulate PreP activity rapidly and selectively, we will provide insight into the involvement of PreP in mitochondria in general and how dysfunction of PreP could lead to diseases.
Subjects/Keywords: Biochemistry; Chemical Biology; Mitochondria; Protease; Small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wijaya, J. (2015). Utilizing Small Molecules to Study Mitochondrial Presequence-Degrading Protease. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/8nm1z5z8
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wijaya, Juwina. “Utilizing Small Molecules to Study Mitochondrial Presequence-Degrading Protease.” 2015. Thesis, UCLA. Accessed January 20, 2021.
http://www.escholarship.org/uc/item/8nm1z5z8.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wijaya, Juwina. “Utilizing Small Molecules to Study Mitochondrial Presequence-Degrading Protease.” 2015. Web. 20 Jan 2021.
Vancouver:
Wijaya J. Utilizing Small Molecules to Study Mitochondrial Presequence-Degrading Protease. [Internet] [Thesis]. UCLA; 2015. [cited 2021 Jan 20].
Available from: http://www.escholarship.org/uc/item/8nm1z5z8.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wijaya J. Utilizing Small Molecules to Study Mitochondrial Presequence-Degrading Protease. [Thesis]. UCLA; 2015. Available from: http://www.escholarship.org/uc/item/8nm1z5z8
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Manchester
4.
Uggenti, Carolina.
Modification of mutant bestrophin-1 processing to prevent retinal degeneration.
Degree: PhD, 2015, University of Manchester
URL: https://www.research.manchester.ac.uk/portal/en/theses/modification-of-mutant-bestrophin1-processing-to-prevent-retinal-degeneration(854430cf-9c14-4142-85f4-8f1594310c05).html
;
http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677814
► Bestrophin-1 is a homopentameric Ca2+-gated anion channel which localises to the basolateral plasma membrane of retinal pigment epithelium (RPE) cells. Homozygous and compound heterozygous mutations…
(more)
▼ Bestrophin-1 is a homopentameric Ca2+-gated anion channel which localises to the basolateral plasma membrane of retinal pigment epithelium (RPE) cells. Homozygous and compound heterozygous mutations in the BEST1 gene are associated with autosomal recessive bestrophinopathy (ARB), a retinopathy characterised by altered electrooculogram (EOG), deposits in the retina, and is often associated with the risk of developing angle-closure glaucoma. The mechanism by which mutations in bestrophin-1 cause disease remains unknown. Expression of four ARB-causing bestrophin-1 proteins in polarised MDCKII cells, a cell model for RPE, results in mutant proteins mislocalisation and degradation. Furthermore, when the ability of the mutant proteins to conduct Cl- ions was investigated in HEK293 cells by whole-cell patch-clamp, a reduction in the Cl- current was observed in all mutants compared to the WT.The use of a combination of the small molecules bortezomib and 4-phenylbutyrate (4PBA) successfully restored the expression and trafficking of all four ARB-causing bestrophin-1 proteins. Importantly, 4PBA was also able to restore the ability of the mutant channel to conduct Cl- ions. Biotinylation of cell surface proteins shows that the number of active channels at the plasma membrane of HEK293 cells increases following 4PBA treatment. The functional rescue achieved with 4PBA supports the hypothesis that ARB-associated missense mutations reduce the number of functional channels that reach the cell membrane rather than altering other aspects of channel function. The results presented in this thesis suggest that 4PBA may be a promising therapy for the treatment of ARB and the other bestrophinopathies resulting from missense mutations in BEST1, particularly as 4PBA is already approved for long-term use in infants and adults. These finding also pave the way for the use of small molecule therapies to treat conformational diseases caused by mutation in other protein expressed in the RPE.
Subjects/Keywords: 617.7; bestrophin-1; small molecules treatment
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Uggenti, C. (2015). Modification of mutant bestrophin-1 processing to prevent retinal degeneration. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/modification-of-mutant-bestrophin1-processing-to-prevent-retinal-degeneration(854430cf-9c14-4142-85f4-8f1594310c05).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677814
Chicago Manual of Style (16th Edition):
Uggenti, Carolina. “Modification of mutant bestrophin-1 processing to prevent retinal degeneration.” 2015. Doctoral Dissertation, University of Manchester. Accessed January 20, 2021.
https://www.research.manchester.ac.uk/portal/en/theses/modification-of-mutant-bestrophin1-processing-to-prevent-retinal-degeneration(854430cf-9c14-4142-85f4-8f1594310c05).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677814.
MLA Handbook (7th Edition):
Uggenti, Carolina. “Modification of mutant bestrophin-1 processing to prevent retinal degeneration.” 2015. Web. 20 Jan 2021.
Vancouver:
Uggenti C. Modification of mutant bestrophin-1 processing to prevent retinal degeneration. [Internet] [Doctoral dissertation]. University of Manchester; 2015. [cited 2021 Jan 20].
Available from: https://www.research.manchester.ac.uk/portal/en/theses/modification-of-mutant-bestrophin1-processing-to-prevent-retinal-degeneration(854430cf-9c14-4142-85f4-8f1594310c05).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677814.
Council of Science Editors:
Uggenti C. Modification of mutant bestrophin-1 processing to prevent retinal degeneration. [Doctoral Dissertation]. University of Manchester; 2015. Available from: https://www.research.manchester.ac.uk/portal/en/theses/modification-of-mutant-bestrophin1-processing-to-prevent-retinal-degeneration(854430cf-9c14-4142-85f4-8f1594310c05).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.677814
5.
Zhang, Man.
Design,
synthesis, and evaluation of bioactive molecules; Chiral
polyvinylpyrrolidones supported Cu/Au nanoclusters catalyzed
cyclization of 5-substituted nona-1,8-dien-5-ols.
Degree: PhD, Department of
Chemistry, 2017, Kansas State University
URL: http://hdl.handle.net/2097/35470
► Small molecules are of great importance in drug discovery currently. The first three chapters discussed the design, synthesis and bio-evaluation of three different classes of…
(more)
▼ Small molecules are of great importance in drug
discovery currently. The first three chapters discussed the design,
synthesis and bio-evaluation of three different classes of
small
molecules and exploration of their biological targets. Triacsin C
analogs were designed as long chain fatty acyl-CoA synthetase
(ACSL) inhibitors for attenuating ischemia and reperfusion (I/R)
injury. Oxadiazole derivatives were designed as T-type calcium
channel inhibitors, which have potential application in the
treatment of seizure and epilepsy. Tricyclic pyrone derivatives
were reported as anti-Alzheimer lead compounds in previous research
done by the Hua group. TP70 and CP2 were synthesized to explore
their pharmacokinetics properties.
Chapter 4 described
chiral-substituted poly-N-vinylpyrrolidones (CSPVP) supported Cu/Au
nanoclusters mediation of cyclization reaction of 5-substituted
nona-1,8-dien-5-ols. A five-member cyclized lactone possessing a
stereogenic tetrasubstituted carbon center was formed in a one-step
Cu/Au nanoclusters-hydrogen peroxide oxidation reaction. This
developed a novel and simple method to synthesize tetrasubstituted
carbon stereogenic center. Drawbacks of the method in my initial
study were low reaction yield and moderate enantioselectivity. The
chemical yield and enantioselectivity have been significantly
improved by introducing bulkier substitution in C3 and C4 positions
of CSPVP according to the updates of ongoing research.
Advisors/Committee Members: Duy H. Hua.
Subjects/Keywords: Bioactive
small molecules; Chiral-substituted
polyvinylpyrrolidones (CSPVP)
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, M. (2017). Design,
synthesis, and evaluation of bioactive molecules; Chiral
polyvinylpyrrolidones supported Cu/Au nanoclusters catalyzed
cyclization of 5-substituted nona-1,8-dien-5-ols. (Doctoral Dissertation). Kansas State University. Retrieved from http://hdl.handle.net/2097/35470
Chicago Manual of Style (16th Edition):
Zhang, Man. “Design,
synthesis, and evaluation of bioactive molecules; Chiral
polyvinylpyrrolidones supported Cu/Au nanoclusters catalyzed
cyclization of 5-substituted nona-1,8-dien-5-ols.” 2017. Doctoral Dissertation, Kansas State University. Accessed January 20, 2021.
http://hdl.handle.net/2097/35470.
MLA Handbook (7th Edition):
Zhang, Man. “Design,
synthesis, and evaluation of bioactive molecules; Chiral
polyvinylpyrrolidones supported Cu/Au nanoclusters catalyzed
cyclization of 5-substituted nona-1,8-dien-5-ols.” 2017. Web. 20 Jan 2021.
Vancouver:
Zhang M. Design,
synthesis, and evaluation of bioactive molecules; Chiral
polyvinylpyrrolidones supported Cu/Au nanoclusters catalyzed
cyclization of 5-substituted nona-1,8-dien-5-ols. [Internet] [Doctoral dissertation]. Kansas State University; 2017. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2097/35470.
Council of Science Editors:
Zhang M. Design,
synthesis, and evaluation of bioactive molecules; Chiral
polyvinylpyrrolidones supported Cu/Au nanoclusters catalyzed
cyclization of 5-substituted nona-1,8-dien-5-ols. [Doctoral Dissertation]. Kansas State University; 2017. Available from: http://hdl.handle.net/2097/35470
University of New South Wales
6.
Mills, Toby.
Diversity and bioactivity of microorganisms associated with Australian stingless bee species.
Degree: Chemistry, 2018, University of New South Wales
URL: http://handle.unsw.edu.au/1959.4/60350
;
https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51889/SOURCE02?view=true
► The rapid emergence and transfer of antimicrobial resistance in pathogenic organisms has greatly reduced our ability to treat clinical microbial infections. To continue to treat…
(more)
▼ The rapid emergence and transfer of antimicrobial resistance in pathogenic organisms has greatly reduced our ability to treat clinical microbial infections. To continue to treat clinical microbial infections in humans and animals it is imperative that we discover new antimicrobial compounds with novel modes of action. The aim of this thesis was to explore the antimicrobial potential of microorganisms associated with three Australian native stingless bees, Tetragonula carbonaria, Austroplebeia australis and Tetragonula hockingsii. Observations of antimicrobial activity from honey, hive materials and whole extracts of Australian stingless bees inspired the hypothesis that the microbiota associated with these stingless bee species could produce bioactive compounds. To address this aim, a comprehensive evaluation of the native bee whole gut microbiome was performed (Chapter 2), with the goal of identifying microorganisms exhibiting specific associations. Guided by these results bacteria and fungi were cultured from the gut and cuticle of three species of Australian stingless bees and screened by genetic and chemical methods to create a subset enriched for chemical diversity and biosynthetic potential (Chapter 3). Biosynthetic potential was correlated to the presence of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) gene clusters due to their historical success as therapeutic natural products and their potential to produce a wide array of bioactive chemical structures. Antimicrobial activity of the selected microbes was assessed by liquid culture bioassay and a successful candidate identified for bioactivity-guided fractionation and compound characterisation (Chapter 4).The antimicrobial long chain fatty acid, 9-hexadecenoic acid, was isolated and characterised from the Xanthomonas sp., TMB - 122. Additional characterisation identified the production of 2,5-di-tert-butylphenol, a phenolic compound with antimicrobial activity, and tridec-1-ene, an acyclic olefin insect pheromone, by Xanthomonas sp., TMB - 122. This investigation confirmed our hypothesis that microbes associated with Australian stingless bees were bioactive. Furthermore the combined genetic and chemical analyses performed validated the selection of candidates possessing PKS and NRPS gene clusters as this methodology accounted for 75% of the chemical diversity observed by LC-MS profiling. The steps enclosed in this thesis are the practical application of the theory that modern drug discovery methods must build on the knowledge off the past whilst continuing to innovate and explore.
Advisors/Committee Members: Donald, William, Chemistry, Faculty of Science, UNSW, Neilan, Brett, Biotechnology & Biomolecular Sciences, Faculty of Science, UNSW.
Subjects/Keywords: Antimicrobial; Stingless bees; Bioactive small molecules; Microbiome
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mills, T. (2018). Diversity and bioactivity of microorganisms associated with Australian stingless bee species. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/60350 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51889/SOURCE02?view=true
Chicago Manual of Style (16th Edition):
Mills, Toby. “Diversity and bioactivity of microorganisms associated with Australian stingless bee species.” 2018. Doctoral Dissertation, University of New South Wales. Accessed January 20, 2021.
http://handle.unsw.edu.au/1959.4/60350 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51889/SOURCE02?view=true.
MLA Handbook (7th Edition):
Mills, Toby. “Diversity and bioactivity of microorganisms associated with Australian stingless bee species.” 2018. Web. 20 Jan 2021.
Vancouver:
Mills T. Diversity and bioactivity of microorganisms associated with Australian stingless bee species. [Internet] [Doctoral dissertation]. University of New South Wales; 2018. [cited 2021 Jan 20].
Available from: http://handle.unsw.edu.au/1959.4/60350 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51889/SOURCE02?view=true.
Council of Science Editors:
Mills T. Diversity and bioactivity of microorganisms associated with Australian stingless bee species. [Doctoral Dissertation]. University of New South Wales; 2018. Available from: http://handle.unsw.edu.au/1959.4/60350 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:51889/SOURCE02?view=true
The Ohio State University
7.
Behnke, Shelby Lee.
Resonance Raman Investigations of [NiFe] Hydrogenase
Models.
Degree: MS, Chemistry, 2016, The Ohio State University
URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1479728987893667
► Hydrogenase (H2ases) enzymes carry out bidirectional hydrogen production and oxidation reactions. To better understand the mechanism of hydrogen conversion, spectroscopic studies on small molecule mimics…
(more)
▼ Hydrogenase (H2ases) enzymes carry out bidirectional
hydrogen production and oxidation reactions. To better understand
the mechanism of hydrogen conversion, spectroscopic studies on
small molecule mimics provide important metrics to correlate
structure and function of the native enzymes. In this work, a
series of molecular complexes that mimic the [NiFe] hydrogenase
have been synthesized with different phosphine ligand substituents
and analyzed using multiple analytical techniques, including
nuclear magnetic resonance, Fourier transform infrared, and
resonance Raman spectroscopies. Three model compounds have been
selected as the focus of this investigation into the vibrational
structure of the [NiFe] active site:
[Ni(dppe)(µ-pdt)(µ-H)Fe(CO)3][BF4],
[Ni(dcpe)(µ-pdt)(µ-H)Fe(CO)3][BF4], and
[Ni(dppbz)(µ-pdt)(µ-H)Fe(CO)3][BF4]. (dppe=
diphenylphosphinoethane, dcpe= dicyclohexylphosphinoethane, and
dppbz= diphenylphosphinobenzene). These compounds have been
previously synthesized and shown to exhibit high activity for
proton reduction but have not been fully characterized
spectroscopically to assess the solution-phase structure of the
metal-hydride core. (Barton et al., 2010, JACS. 132, 14877-14885.)
Specifically, resonance Raman (RR) spectroscopy was used to study
the vibrational bands of each of the
molecules, which were then
assigned to specific normal modes of the molecule. The
[Ni(dppe)(µ-pdt)(µ-H)Fe(CO)3]BF4 compound has been previously
studied in great detail by RR, and this molecule was used as a
template from which to understand the structures of the series. It
was found that perturbations of ligands on the metal center alter
the molecular vibrations, particularly of the metal-hydride core.
This work provides important metrics for comparison between
synthetic and the natural enzyme systems, with the intention of
better understanding the mechanisms of native hydrogenases and
informing next-generation catalyst design.
Advisors/Committee Members: Shafaat, Hannah (Advisor).
Subjects/Keywords: Chemistry; Resonance Raman; Spectroscopy; Hydrogenase; small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Behnke, S. L. (2016). Resonance Raman Investigations of [NiFe] Hydrogenase
Models. (Masters Thesis). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1479728987893667
Chicago Manual of Style (16th Edition):
Behnke, Shelby Lee. “Resonance Raman Investigations of [NiFe] Hydrogenase
Models.” 2016. Masters Thesis, The Ohio State University. Accessed January 20, 2021.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1479728987893667.
MLA Handbook (7th Edition):
Behnke, Shelby Lee. “Resonance Raman Investigations of [NiFe] Hydrogenase
Models.” 2016. Web. 20 Jan 2021.
Vancouver:
Behnke SL. Resonance Raman Investigations of [NiFe] Hydrogenase
Models. [Internet] [Masters thesis]. The Ohio State University; 2016. [cited 2021 Jan 20].
Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1479728987893667.
Council of Science Editors:
Behnke SL. Resonance Raman Investigations of [NiFe] Hydrogenase
Models. [Masters Thesis]. The Ohio State University; 2016. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1479728987893667
University of Edinburgh
8.
Marie, Kerrie Leanne.
Chemical and genetic control of melanocyte development, proliferation and regeneration in zebrafish.
Degree: PhD, 2013, University of Edinburgh
URL: http://hdl.handle.net/1842/11821
► Melanocytes are pigment-producing cells that colour our hair, skin and eyes. Melanocytes are evolutionary conserved in vertebrates, and in addition to contributing to pigmentation and…
(more)
▼ Melanocytes are pigment-producing cells that colour our hair, skin and eyes. Melanocytes are evolutionary conserved in vertebrates, and in addition to contributing to pigmentation and pattern formation, can contribute to background adaptation (zebrafish) and protection against harmful UV irradiation (humans). Many of the processes involved in melanocyte development – such as migration, proliferation and differentiation - are misregulated in melanoma. Here, I use chemical biology in zebrafish to identify targetable pathways in melanocyte development and regeneration, with a view to how these processes may be misregulated in melanoma and other pigmentation syndromes. We first wanted to address the potential for small molecules to regulate multiple stages of melanocyte development and differentiation. In Chapter 3, I describe my work involved in a small molecule screen for clinically active compounds that alter melanocyte biology (Colanesi et al., 2012). In this work we have identified small-molecules that affect melanocyte migration, differentiation, survival, morphology and number. This is important as it highlights new pathways essential for normal melanocyte development and consequently provides further tools in which to study melanocytes. Identifying the target of small molecules in vivo is a challenge in chemical biology. In Chapter 4, I describe my contributions to understanding how 5-nitrofuran compounds act in zebrafish (Zhou et al., 2012). My work has contributed to understanding the activity of 5-nitrofurans is dependent upon its nitrofuran ring structure. I have also helped confirm a conserved interaction between 5-nitrofurans and ALDH2, which may contribute to the off-target effects observed in the clinic. These results are important as they aid further understand of the 5-nitrofuran class of drugs and give evidence to support combination therapy of 5-nitrofurans with ALDH2 inhibitors as a way to overcome clinical side effects. Additionally I show that NFN1 treatment limits ensuing melanocyte regeneration thereby suggesting a role at the Melanocyte Stem Cell (MSC), which provides me with a key tool to study melanocyte regeneration in zebrafish. How tissue specific cell numbers are specified and maintained is a key question in developmental biology. In Chapter 5, I describe the identification of the MITF gene in the maintenance of cell cycle arrest in differentiated melanocytes (Taylor et al., 2011). We show that the human melanoma mutation MITF4TΔ2B promotes melanocyte division, thereby suggesting a role for melanocyte division in the pathogenesis of melanoma. This work is valuable because it highlights Mitf as a molecular rheostat that controls melanocyte proliferation and differentiation in living vertebrates, and helps us to understand the role of MITF in melanoma progression. Little is known about the pathways that control melanocyte stem cells in animals. To identify new melanocyte stem cell pathways, I used NFN1 as the basis for a small molecule screen for enhancers of melanocyte regeneration (Chapter…
Subjects/Keywords: 616.99; zebrafish; small-molecules; small molecule screen; melanocyte; development; regeneration
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Marie, K. L. (2013). Chemical and genetic control of melanocyte development, proliferation and regeneration in zebrafish. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/11821
Chicago Manual of Style (16th Edition):
Marie, Kerrie Leanne. “Chemical and genetic control of melanocyte development, proliferation and regeneration in zebrafish.” 2013. Doctoral Dissertation, University of Edinburgh. Accessed January 20, 2021.
http://hdl.handle.net/1842/11821.
MLA Handbook (7th Edition):
Marie, Kerrie Leanne. “Chemical and genetic control of melanocyte development, proliferation and regeneration in zebrafish.” 2013. Web. 20 Jan 2021.
Vancouver:
Marie KL. Chemical and genetic control of melanocyte development, proliferation and regeneration in zebrafish. [Internet] [Doctoral dissertation]. University of Edinburgh; 2013. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1842/11821.
Council of Science Editors:
Marie KL. Chemical and genetic control of melanocyte development, proliferation and regeneration in zebrafish. [Doctoral Dissertation]. University of Edinburgh; 2013. Available from: http://hdl.handle.net/1842/11821
9.
Yadav, Seema.
Complexes of metal ion with small doner groups
molecules; -.
Degree: Chemistry, 2012, Aligarh Muslim University
URL: http://shodhganga.inflibnet.ac.in/handle/10603/28616
non
Bibliography page is at the end of each
chapter.
Advisors/Committee Members: Siddiq, K.S.Subjects/Keywords: Metal Ion; Small Doner ,; Molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yadav, S. (2012). Complexes of metal ion with small doner groups
molecules; -. (Thesis). Aligarh Muslim University. Retrieved from http://shodhganga.inflibnet.ac.in/handle/10603/28616
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Yadav, Seema. “Complexes of metal ion with small doner groups
molecules; -.” 2012. Thesis, Aligarh Muslim University. Accessed January 20, 2021.
http://shodhganga.inflibnet.ac.in/handle/10603/28616.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yadav, Seema. “Complexes of metal ion with small doner groups
molecules; -.” 2012. Web. 20 Jan 2021.
Vancouver:
Yadav S. Complexes of metal ion with small doner groups
molecules; -. [Internet] [Thesis]. Aligarh Muslim University; 2012. [cited 2021 Jan 20].
Available from: http://shodhganga.inflibnet.ac.in/handle/10603/28616.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yadav S. Complexes of metal ion with small doner groups
molecules; -. [Thesis]. Aligarh Muslim University; 2012. Available from: http://shodhganga.inflibnet.ac.in/handle/10603/28616
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
10.
Del Rio, Natalia.
Germylène P,N-hétérocyclique : synthèse et réactivité : P,N-heterocyclic germylene : synthesis and reactivity.
Degree: Docteur es, Chimie organométallique de coordination, 2016, Université Toulouse III – Paul Sabatier
URL: http://www.theses.fr/2016TOU30319
► Ce travail de thèse est axé sur la synthèse et la réactivité d'un nouveau germylène P,N-hétérocyclique stabilisé par un fragment phosphanylidène-phosphorane. Le premier chapitre constitue…
(more)
▼ Ce travail de thèse est axé sur la synthèse et la réactivité d'un nouveau germylène P,N-hétérocyclique stabilisé par un fragment phosphanylidène-phosphorane. Le premier chapitre constitue un état de l'art des études portant sur la réactivité des espèces dérivées du groupe principal vis-à-vis de petites molécules (H2, NH3, éthylène, etc.). Une emphase particulière a été apportée à la description des différents mécanismes impliqués dans l'activation des liaisons de hautes énergies et à leur comparaison avec ceux rencontrés dans le cas des métaux de transitions. Le deuxième chapitre présente la synthèse et la caractérisation complète de germylene-phosphacétènes stabilisés par différents ligands phosphine fonctionnalisés. Ces dérivés sont thermiquement labiles et leur décarbonylation à diverse températures conduit au germylène-phosphinidène transitoire correspondant. L'évolution de ces intermédiaires est étroitement liée à la nature du ligand phosphine coordinné au Ge(II) central et, dans le cas du germylène stabilisé par un ligand diaminophosphine à quatre chaînons très volumineux, une migration intramoléculaire conduisant à un nouveau germylène cyclique à six chaînons est observée. L'étude de ce germylène P,N-hétérocyclique fait l'objet du troisième chapitre de ce manuscrit. Ce germylène présente un écart énergétique HOMO-LUMO faible du fait de sa stabilisation par le fragment phosphanilidène-phosphorane. En conséquence, sa réactivité est accrue en comparaison des germylènes N-hétérocycliques classiques pour qui l'écart d'énergie singulet-triplet est supérieur. La réactivité de ce nouveau germylène, incluant une étude en chimie de coordination vers acides de Lewis, est présentée. Dans le quatrième chapitre, un adduit réactif du germylène P,N-hétérocyclique avec un borane a été étudié expérimental et théoriquement. Du fait de l'existence de plusieurs sites réactifs de différentes natures au sein de ce composé, il se comporte comme un système "multi-activation" vis-à-vis de petites molécules. Son utilisation en tant que catalyseur dans des transformations organiques sera également présentée.
The synthesis and reactivity of a new P,N-heterocyclic germylene, stabilized by a phosphanylidene-phosphorane moiety, are the subjects of this work. In the first chapter, a bibliographic study resumes the state of the art of principal main-group systems capable to activate small molecules, such as H2, NH3, ethylene, etc. following similar activation mechanism that those of transition metal complexes. The second chapter present the synthesis and full characterization of stable phosphaketenes functionalized germylenes supported by different phosphine ligands. These derivatives are thermally labile and easily undergo thermal decarbonylation, affording the corresponding transient germylene-phosphinidene. The evolution of these intermediates is strongly related to the nature of the phosphine ligand coordinated to the Ge(II) centre and, in the case of the germylene stabilized by the bulkier four-membered cyclic diamino-phosphine, the…
Advisors/Committee Members: Kato, Tsuyoshi (thesis director).
Subjects/Keywords: Germylène; Réactivité; Petites molécules; Germylene; Reactivity; Small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Del Rio, N. (2016). Germylène P,N-hétérocyclique : synthèse et réactivité : P,N-heterocyclic germylene : synthesis and reactivity. (Doctoral Dissertation). Université Toulouse III – Paul Sabatier. Retrieved from http://www.theses.fr/2016TOU30319
Chicago Manual of Style (16th Edition):
Del Rio, Natalia. “Germylène P,N-hétérocyclique : synthèse et réactivité : P,N-heterocyclic germylene : synthesis and reactivity.” 2016. Doctoral Dissertation, Université Toulouse III – Paul Sabatier. Accessed January 20, 2021.
http://www.theses.fr/2016TOU30319.
MLA Handbook (7th Edition):
Del Rio, Natalia. “Germylène P,N-hétérocyclique : synthèse et réactivité : P,N-heterocyclic germylene : synthesis and reactivity.” 2016. Web. 20 Jan 2021.
Vancouver:
Del Rio N. Germylène P,N-hétérocyclique : synthèse et réactivité : P,N-heterocyclic germylene : synthesis and reactivity. [Internet] [Doctoral dissertation]. Université Toulouse III – Paul Sabatier; 2016. [cited 2021 Jan 20].
Available from: http://www.theses.fr/2016TOU30319.
Council of Science Editors:
Del Rio N. Germylène P,N-hétérocyclique : synthèse et réactivité : P,N-heterocyclic germylene : synthesis and reactivity. [Doctoral Dissertation]. Université Toulouse III – Paul Sabatier; 2016. Available from: http://www.theses.fr/2016TOU30319
UCLA
11.
Douglas, Colin Joseph.
Investigation and Characterization of Small Molecule Modulators for Mitochondrial Processing Peptidase.
Degree: Biochemistry & Molecular Biology, 2014, UCLA
URL: http://www.escholarship.org/uc/item/9th259qj
► Mitochondria are an extremely complex organelle comprised of four discrete compartments and are vital for the proper functioning of key cellular pathways including, energy production,…
(more)
▼ Mitochondria are an extremely complex organelle comprised of four discrete compartments and are vital for the proper functioning of key cellular pathways including, energy production, growth, differentiation, and cellular signaling. The mitochondrial genome encodes for 13 proteins, however the mitochondrial proteome is estimated to contain approximately 600- 1000 proteins; most of these must be imported from the cytosol. Depending on a protein's intended location, there are host signals and import machinery that ensure the correct appropriate localization. Proteins destined for the mitochondrial matrix typically possess a mitochondrial targeting sequence (MTS) found at the N-terminus. These proteins are funneled through the translocon of the outer membrane (TOM complex), the translocon of the inner membrane (TIM23 complex) into the matrix. Here, the MTS is cleaved off by mitochondrial processing peptidase (MPP), allowing the mature protein to fold into its native confirmation.Many proteins, such as MPP, are essential for life, therefore it is difficult to study them using classical approaches or through methods such as RNAi as these may cause global side- effects and take a great deal of time for effect manifestation. As such, our lab devises ways to bypass these issues through the development of small molecule modulators for our proteins of interest. For MPP, this was accomplished through a high-throughput screen (HTS) of approximately 130,000 compounds at UCLA's CNSI screening center.We focused on 2 molecules resulting from the screen, MitoBloCK-50 and -51, which were found to be inhibitors of MPP. Both compounds possess many similarities in the effects we see via MPP inhibition including cleavage of Su9-DHFR, import of Su9-DHFR, import of Cpn10, hPink1 import, and the import of CytB2-DHFR (1-167). Conversely, we also saw differences in their inhibition of MPP and their effect on downstream pathways including, the import of CytC1, the import of CytB2-DHFR (A63P), Parkin recruitment on the surface of mitochondria, and zebrafish development. These similarities and differences between the 2 MitoBloCK compounds could signify differences in their binding and inhibition of MPP, and these differences result in slightly different downstream effects. Overall, we have discovered and initated the characterization of two MPP inhibitors and their respective analogs, potentially helping to elucidate the Pink1-Parkin mitochondrial degradation pathway and the pathways involved in copper metabolism, melanogenesis, and melanin formation.
Subjects/Keywords: Biochemistry; high throughput screen; mitochondria; mitochondrial import; MPP; small molecules; zebrafish
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Douglas, C. J. (2014). Investigation and Characterization of Small Molecule Modulators for Mitochondrial Processing Peptidase. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/9th259qj
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Douglas, Colin Joseph. “Investigation and Characterization of Small Molecule Modulators for Mitochondrial Processing Peptidase.” 2014. Thesis, UCLA. Accessed January 20, 2021.
http://www.escholarship.org/uc/item/9th259qj.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Douglas, Colin Joseph. “Investigation and Characterization of Small Molecule Modulators for Mitochondrial Processing Peptidase.” 2014. Web. 20 Jan 2021.
Vancouver:
Douglas CJ. Investigation and Characterization of Small Molecule Modulators for Mitochondrial Processing Peptidase. [Internet] [Thesis]. UCLA; 2014. [cited 2021 Jan 20].
Available from: http://www.escholarship.org/uc/item/9th259qj.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Douglas CJ. Investigation and Characterization of Small Molecule Modulators for Mitochondrial Processing Peptidase. [Thesis]. UCLA; 2014. Available from: http://www.escholarship.org/uc/item/9th259qj
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Rochester
12.
Ofori, Leslie Odame (1980 - ).
Solving the problem of sequence selective RNA recognition
by small molecules with application to Myotonic Dystrophy and
HIV.
Degree: PhD, 2013, University of Rochester
URL: http://hdl.handle.net/1802/26491
► Synthetic small molecules that bind specific RNA sequences with high affinity are essential biochemical probes for understanding cellular process and as therapeutic agents for treatment…
(more)
▼ Synthetic small molecules that bind specific RNA
sequences with high affinity are essential biochemical probes for
understanding cellular process and as therapeutic agents for
treatment of diseases. This is in part because ribonucleic acid
(RNA) is not simply an intermediary between DNA and protein
biosynthesis. Rather, RNA plays a central role in biochemical
processes including enzyme catalysis, protein translation,
transcription or posttranscriptional regulation of gene expression
and in many disease states. However the ability to design small
molecules to selectively bind RNA sequences and elicit
RNA-dependent biological responses is still an unsolved topic in
bioorganic chemistry.
This thesis describes a strategy to
transform small molecules identified from a Resin Bound Dynamic
Chemistry (RBDCC) library into high affinity and sequence selective
RNA-ligands with in vitro and in vivo activities. This strategy was
tested using a CUG trinucleotide repeat (implicated in Myotonic
Dystrophy type 1) and an HIV-1 frameshift inducing RNA (relevant
for effective translation of gag and pol gene during HIV
replication) as models.
Introduction of a benzo[g]quinoline
substructure previously unknown in the context of RNA recognition,
as well as other modifications, provided several molecules with
enhanced binding properties, including compounds with strong
selectivity for CUG repeats over CAG repeats or CAG-CUG duplex RNA.
Compounds readily penetrate cells, and improve luciferase activity
in a mouse myoblast assay in which enzyme function is coupled to a
release of nuclear CUG-RNA retention. Most importantly, two
compounds are able to partially restore splicing in a mouse model
of DM1. In a parallel effort, the natural product lomofungin was
identified in a high throughput screen as potent inhibitor of the
MBNL-CUG repeat RNA interaction. Analysis of lomofungin showed that
it degraded in DMSO to form a dimer that was 17-fold more active
than lomofungin. In the context of HIV-1, the transformed compounds
stimulated frameshifting in HIV-1 by > 50 % as measured by a
dual luciferase frameshift assay in transiently transfected HEK 293
FT cells. Importantly, this increased frameshifting translated into
a significant inhibition of viral infectivity in pseudotyped
HIV.
Subjects/Keywords: Binding constant; Myotonic Dystrophy; RNA; Small molecules; Selectivity
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ofori, L. O. (. -. ). (2013). Solving the problem of sequence selective RNA recognition
by small molecules with application to Myotonic Dystrophy and
HIV. (Doctoral Dissertation). University of Rochester. Retrieved from http://hdl.handle.net/1802/26491
Chicago Manual of Style (16th Edition):
Ofori, Leslie Odame (1980 - ). “Solving the problem of sequence selective RNA recognition
by small molecules with application to Myotonic Dystrophy and
HIV.” 2013. Doctoral Dissertation, University of Rochester. Accessed January 20, 2021.
http://hdl.handle.net/1802/26491.
MLA Handbook (7th Edition):
Ofori, Leslie Odame (1980 - ). “Solving the problem of sequence selective RNA recognition
by small molecules with application to Myotonic Dystrophy and
HIV.” 2013. Web. 20 Jan 2021.
Vancouver:
Ofori LO(-). Solving the problem of sequence selective RNA recognition
by small molecules with application to Myotonic Dystrophy and
HIV. [Internet] [Doctoral dissertation]. University of Rochester; 2013. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1802/26491.
Council of Science Editors:
Ofori LO(-). Solving the problem of sequence selective RNA recognition
by small molecules with application to Myotonic Dystrophy and
HIV. [Doctoral Dissertation]. University of Rochester; 2013. Available from: http://hdl.handle.net/1802/26491
University of Alberta
13.
Chu, Carmen Y.S.
Rescue of Kidney Anion Exchanger 1 Trafficking
Mutants.
Degree: MS, Department of Physiology, 2012, University of Alberta
URL: https://era.library.ualberta.ca/files/xs55md05p
► The kidney anion exchanger 1 (kAE1) is crucial in the regulation of physiological pH by facilitating Cl-/HCO3- exchange. Inability to do so results in distal…
(more)
▼ The kidney anion exchanger 1 (kAE1) is crucial in the
regulation of physiological pH by facilitating Cl-/HCO3- exchange.
Inability to do so results in distal renal tubular acidosis (dRTA),
which is more often due to mutations leading to mis-localization of
kAE1, rather than complete abolishment of its functional activity.
The purpose of this thesis is to understand the trafficking,
turnover, and rescue of wildtype (WT) and trafficking mutants of
the kAE1. Chemical chaperones and low temperature treatments were
studied for their ability to rescue trafficking of G701D, C479W and
R589H kAE1 mutants. G701D kAE1 was rescued by dimethyl sulfoxide
(DMSO) and is functional at the membrane. The turnover of all kAE1
mutants studied was dependent on the proteasomal pathway, while
G701D and WT kAE1 are also degraded via the lysosomal pathway.
These studies provide essential information for developing rescue
methods at the molecular level, targeting the source of the disease
rather than the symptoms.
Subjects/Keywords: Trafficking; Anion Exchanger; Degradation; Rescue; Chemicals; Small molecules; Kidney
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chu, C. Y. S. (2012). Rescue of Kidney Anion Exchanger 1 Trafficking
Mutants. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/xs55md05p
Chicago Manual of Style (16th Edition):
Chu, Carmen Y S. “Rescue of Kidney Anion Exchanger 1 Trafficking
Mutants.” 2012. Masters Thesis, University of Alberta. Accessed January 20, 2021.
https://era.library.ualberta.ca/files/xs55md05p.
MLA Handbook (7th Edition):
Chu, Carmen Y S. “Rescue of Kidney Anion Exchanger 1 Trafficking
Mutants.” 2012. Web. 20 Jan 2021.
Vancouver:
Chu CYS. Rescue of Kidney Anion Exchanger 1 Trafficking
Mutants. [Internet] [Masters thesis]. University of Alberta; 2012. [cited 2021 Jan 20].
Available from: https://era.library.ualberta.ca/files/xs55md05p.
Council of Science Editors:
Chu CYS. Rescue of Kidney Anion Exchanger 1 Trafficking
Mutants. [Masters Thesis]. University of Alberta; 2012. Available from: https://era.library.ualberta.ca/files/xs55md05p
University of Michigan
14.
Wong, Jenny-Marie.
Liquid Chromatography-Mass Spectrometry Strategies for in vivo Neurochemical Monitoring with Microdialysis.
Degree: PhD, Chemistry, 2016, University of Michigan
URL: http://hdl.handle.net/2027.42/135792
► Liquid chromatography mass spectrometry (LC-MS) is a powerful analytical tool for multi-analyte quantification. This method can be combined with microdialysis sampling to study small molecules…
(more)
▼ Liquid chromatography mass spectrometry (LC-MS) is a powerful analytical tool for multi-analyte quantification. This method can be combined with microdialysis sampling to study
small molecules and neuropeptides within discrete brain regions. This thesis focuses on the development of targeted LC-MS assays to analyze dialysate samples collected from awake animals to correlate neurochemical dynamics with behavior.
Previous LC-MS assays used benzoyl chloride derivatization to enable quantification of 17 neurotransmitters and metabolites in dialysate samples. In this work, derivatization conditions were modified to improve sensitivity up to 25-fold and reduce complexity of the procedure. The assay was also expanded to 70 compounds including amino acids, polyamines (e.g., putrescine, spermidine, spermine), compounds from catecholamine biosynthesis pathways (e.g., tyrosine and tryptophan metabolic pathways), and trace amines (e.g., tyramine, octopamine, synephrine). Besides measurements in dialysate, the method was able to analyze plasma and cerebrospinal fluid samples. This work improves the utility of benzoyl chloride, which labels multiple important functional groups, for widely targeted metabolomics methods.
Neuropeptides constitute the largest group of neurotransmitters in the central nervous system. Neuropeptide signaling is involved in many physiological functions but detection in vivo is challenging due to low picomolar concentrations. Targeted capillary LC-MS methods were developed for neurotensin, oxytocin, dynorphin, and enkephalins. The assays utilize desalting and preconcentration on a single analytical column to achieve low picomolar limits of detection. Detection was improved by optimizing all facets of neuropeptide handling from sampling to detection with capillary LC-MS.
These techniques were applied to examine several aspects of neuronal function. Specific neuronal circuits were defined, confirmed, and targeted by combining these analytical tools with pharmacogenetic and optogenetic methods. Novel pathophysiological changes to opioid neuropeptide (dynorphin and enkephalins) dynamics were elucidated in a rat model of Parkinson’s disease, and a potential neuropeptide-based treatment was established to reduce the abnormal dyskinetic movements associated with chronic dopamine replacement therapies in Parkinson’s Disease. These new multiplexed approaches will advance our understanding of the complex processes underlying neuronal function at the molecular and circuit levels, as well as provides an improved set of experimental tools to better understand lingering questions in the field of neuroscience.
Advisors/Committee Members: Kennedy, Robert T (committee member), Myers, Martin (committee member), Hakansson, Kristina I (committee member), Meyerhoff, Mark E (committee member).
Subjects/Keywords: liquid chromatography mass spectrometry neuropeptides and small molecules; Chemistry; Science
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wong, J. (2016). Liquid Chromatography-Mass Spectrometry Strategies for in vivo Neurochemical Monitoring with Microdialysis. (Doctoral Dissertation). University of Michigan. Retrieved from http://hdl.handle.net/2027.42/135792
Chicago Manual of Style (16th Edition):
Wong, Jenny-Marie. “Liquid Chromatography-Mass Spectrometry Strategies for in vivo Neurochemical Monitoring with Microdialysis.” 2016. Doctoral Dissertation, University of Michigan. Accessed January 20, 2021.
http://hdl.handle.net/2027.42/135792.
MLA Handbook (7th Edition):
Wong, Jenny-Marie. “Liquid Chromatography-Mass Spectrometry Strategies for in vivo Neurochemical Monitoring with Microdialysis.” 2016. Web. 20 Jan 2021.
Vancouver:
Wong J. Liquid Chromatography-Mass Spectrometry Strategies for in vivo Neurochemical Monitoring with Microdialysis. [Internet] [Doctoral dissertation]. University of Michigan; 2016. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2027.42/135792.
Council of Science Editors:
Wong J. Liquid Chromatography-Mass Spectrometry Strategies for in vivo Neurochemical Monitoring with Microdialysis. [Doctoral Dissertation]. University of Michigan; 2016. Available from: http://hdl.handle.net/2027.42/135792
Vanderbilt University
15.
Cross, Emily Elizabeth.
Studies on the Molecular Regulation of Epicardial Cell Movement.
Degree: PhD, Cell and Developmental Biology, 2012, Vanderbilt University
URL: http://hdl.handle.net/1803/10483
► Epicardial development is a complex process that involves tightly regulated coordination of concurrent cellular behaviors ranging from sheet migration to secretion. The regulation of these…
(more)
▼ Epicardial development is a complex process that involves tightly regulated coordination of concurrent cellular behaviors ranging from sheet migration to secretion. The regulation of these behaviors is poorly understood, and epicardial cell biological studies will improve the understanding of heart development and subsequent function. Here, a novel
small organic molecule screening methodology of epicardial behaviors is used to elucidate regulatory relationships governing this developmental program. As proof-of-principle, a novel signaling relationship was identified in which TGFβ and BMP signal cascades cooperatively regulate epicardial sheet migration. It is further demonstrated here that epicardial cells participate in a newly identified cellular behavior: regulated cell movement through autocrine extracellular matrix (ECM) deposition. The studies identify two novel regulators of autocrine ECM deposition, Bves and NDRG4. Additionally, we demonstrate that Bves regulates cell surface trafficking of the focal adhesion component β1-integrin through an interaction with VAMP3, a v-SNARE recycling endosome component. These studies in combination with previous work indicate that Bves functions in epicardial cells and globally to traffic adhesion components to the cell surface. This positions Bves as a general regulator of cell-cell and cell-matrix adhesion. Taken together, these studies elucidate regulation of epicardial cell behaviors, reveal a novel epicardial behavior, and suggest a global mechanism for Bves diverse effects of development and disease.
Advisors/Committee Members: Alissa Weaver (committee member), David Bader (committee member), Sandra Zinkel (committee member), Matthew Tyska (committee member), H. Scott Baldwin (Committee Chair).
Subjects/Keywords: Small Organic Molecules; NDRG4; Bves; migration; cell biology; heart
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cross, E. E. (2012). Studies on the Molecular Regulation of Epicardial Cell Movement. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10483
Chicago Manual of Style (16th Edition):
Cross, Emily Elizabeth. “Studies on the Molecular Regulation of Epicardial Cell Movement.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021.
http://hdl.handle.net/1803/10483.
MLA Handbook (7th Edition):
Cross, Emily Elizabeth. “Studies on the Molecular Regulation of Epicardial Cell Movement.” 2012. Web. 20 Jan 2021.
Vancouver:
Cross EE. Studies on the Molecular Regulation of Epicardial Cell Movement. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1803/10483.
Council of Science Editors:
Cross EE. Studies on the Molecular Regulation of Epicardial Cell Movement. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/10483
Vanderbilt University
16.
Williams, Charles Houston III.
Chemical genetics of Vertebrate development.
Degree: PhD, Cell and Developmental Biology, 2017, Vanderbilt University
URL: http://hdl.handle.net/1803/10641
► Small molecules have value in their ability to modulate protein activity in ways that are not accessible using conventional genetic methods, and their potential to…
(more)
▼ Small molecules have value in their ability to modulate protein activity in ways that are not accessible using conventional genetic methods, and their potential to be developed into therapeutics. As genetic causes of human disease are identified, many are found to play an integral role in embryonic development as well. The purpose of this dissertation is to utilize vertebrate embryonic development as a platform for discovery and characterization of chemical probes using phenotype guided development. I discovered three
molecules, Eggmanone, Incaskin, and Ogremorphin based on ability to perturb development of a composite of 29 anatomical features. Using these anatomical features as a query against the wealth of reference genotype-phenotype data in ZFIN, I identified the targets of the
small molecules as PDE4, CK2α, and GPR68. Using eggmanone, I characterize a novel role for PDE4 in regulation of HH signaling, and show that it could be a useful therapeutic target for smo inhibitor resistant cancers. Using incaskin, I show an unbiased phenotypic clustering methodology for target deconvolution; furthermore, I show that incaskin is a highly selective, potent CK2α inhibitor which provides a therapeutic approach for targeting cancers down stream of APC in Wnt signaling. Using ogremorphin, a first in class inhibitor of GPR68, I show that proton sensing GPR68 is critical neural crest migration. Furthermore, I show that proton-sensing GPR68 represents a novel chemically tractably therapeutic avenue for development of an anti-metastatic agent. This body of work contributes to novel discovery of
small molecules, signaling, and developmental biology
Advisors/Committee Members: David Bader (committee member), Craig Lindsley (committee member), Charles C Hong (committee member), Ken Lau (committee member), Guoqiang Gu (Committee Chair).
Subjects/Keywords: Signalling pathways; Developmental Biology; Chemical Biology; small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Williams, C. H. I. (2017). Chemical genetics of Vertebrate development. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10641
Chicago Manual of Style (16th Edition):
Williams, Charles Houston III. “Chemical genetics of Vertebrate development.” 2017. Doctoral Dissertation, Vanderbilt University. Accessed January 20, 2021.
http://hdl.handle.net/1803/10641.
MLA Handbook (7th Edition):
Williams, Charles Houston III. “Chemical genetics of Vertebrate development.” 2017. Web. 20 Jan 2021.
Vancouver:
Williams CHI. Chemical genetics of Vertebrate development. [Internet] [Doctoral dissertation]. Vanderbilt University; 2017. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1803/10641.
Council of Science Editors:
Williams CHI. Chemical genetics of Vertebrate development. [Doctoral Dissertation]. Vanderbilt University; 2017. Available from: http://hdl.handle.net/1803/10641
Penn State University
17.
Ramadoss, Nitya S.
The trans-translation pathway as a target for broad-spectrum antibacterial development.
Degree: 2013, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/17352
► One of many current, pressing concerns on a global scale regarding public health, is the emergence of multi-drug resistant pathogens that cause a number of…
(more)
▼ One of many current, pressing concerns on a global scale regarding public health, is the emergence of multi-drug resistant pathogens that cause a number of hospital-acquired and community-borne diseases. The problem is aggravated by the fact that there are not enough new drugs available to combat these pathogens or re-sensitize them to existing therapies. As a consequence, there is an ongoing quest for new targets and new drugs.
One such target described in this study is the trans-translation pathway, the key components of which are ubiquitous among bacteria. The pathway, mediated by the tmRNA- SmpB ribonucleoprotein complex, serves to release translational complexes that stall at the 3’- end of nonstop mRNAs, and ensures removal of both the aberrant mRNA and incomplete nascent polypeptide. The presence of tmRNA-SmpB in every bacterial species suggests that trans-translation confers some competitive advantage to the cell. Most likely, all bacteria require the resolution of nonstop translational complexes to be able to survive and carry out vital cellular processes. The idea is supported by results obtained in this study from examining the role of trans-translation in pathogen Shigella flexneri, and its close relative Escherichia coli. It has been shown that tmRNA is not essential in E. coli, because it has an alternate factor, ArfA, which mediates the release of nonstop ribosomes. This study shows that tmRNA cannot be deleted in S. flexneri, which lacks ArfA. However, this phenotype is suppressed by providing S. flexneri cells with E. coli ArfA, indicating that due to the absence of a functional backup ribosome release mechanism, tmRNA is essential in S. flexneri.
Establishing the requirement for tmRNA in S. flexneri has added to existing knowledge about the role of trans-translation in the viability and virulence of a number of other pathogens. The phenotypes that occur in pathogens due to lack of tmRNA activity, together with the fact that the components of trans-translation are not found in animals, makes the pathway additionally attractive as a drug target. This study validates the pathway as a target for broad- spectrum antibacterial development. High throughput screening and secondary screening methods were used to identify
small molecule inhibitors of trans-translation, several of which exhibited antibacterial activity against three different bacterial species. In S. flexneri, inhibition of bacterial growth by trans-translation inhibitors was consistent with the species requiring the pathway for survival. One of the several compounds exhibiting broad-spectrum activity, KKL- 35, which scored as a tagging inhibitor in both E. coli and in Mycobacterium smegmatis, also inhibited tmRNA-mediated tagging in vitro. Attempts to isolate mutant S. flexneri strains resistant to KKL-35 were largely unsuccessful, suggesting that KKL-35 may target a component within the cell in a manner that could select against the development of resistance to the inhibitor. Taken together, this work establishes the foundations for…
Advisors/Committee Members: Kenneth Charles Keiler, Dissertation Advisor/Co-Advisor, Kenneth Charles Keiler, Committee Chair/Co-Chair, Sarah Ellen Ades, Committee Member, Squire J Booker, Committee Member, Katsuhiko Murakami, Committee Member, Edward G Dudley, Committee Member.
Subjects/Keywords: trans-translation; tmRNA; antibiotic development; small molecules; Shigella flexneri
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ramadoss, N. S. (2013). The trans-translation pathway as a target for broad-spectrum antibacterial development. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17352
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ramadoss, Nitya S. “The trans-translation pathway as a target for broad-spectrum antibacterial development.” 2013. Thesis, Penn State University. Accessed January 20, 2021.
https://submit-etda.libraries.psu.edu/catalog/17352.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ramadoss, Nitya S. “The trans-translation pathway as a target for broad-spectrum antibacterial development.” 2013. Web. 20 Jan 2021.
Vancouver:
Ramadoss NS. The trans-translation pathway as a target for broad-spectrum antibacterial development. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Jan 20].
Available from: https://submit-etda.libraries.psu.edu/catalog/17352.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ramadoss NS. The trans-translation pathway as a target for broad-spectrum antibacterial development. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/17352
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Penn State University
18.
Hernandez Borrero, Liz Janice.
Anti-tumor effect and destabilization of mutant p53 by CB002, a p53-pathway restoring small molecule that stimulates autophagy.
Degree: 2016, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/13038ljh216
► Tumor suppressor p53 mediates genotoxic and cellular stress signals by controlling cell fate through transcriptional activation of genes involved in DNA repair, cell cycle arrest,…
(more)
▼ Tumor suppressor p53 mediates genotoxic and cellular stress signals by controlling cell fate through transcriptional activation of genes involved in DNA repair, cell cycle arrest, cell senescence, and apoptosis. p53 is mutated in over half of human cancers and this is associated with tumor development and chemotherapy resistance. Mutations in p53 are mostly found in the DNA-binding domain and they prevent p53 to exert its normal tumor suppressive functions. Furthermore, p53 mutations can result in gain-of-function activity, acquiring oncogenic characteristics. Therefore, altering the stability of mutant p53 protein is an attractive therapeutic strategy in cancer cells. The current project aims to identify compounds that restore the p53 pathway and modulate mutant p53 protein. Accordingly, we used a luciferase based p53 reporter to screen for
small molecules that restore the p53 pathway in mutant p53-bearing cancer cells. We identified a
small molecule, CB002, as a candidate for restoration of the p53 pathway in mutant p53-harboring cancer cells.
Colorectal cancer cell lines SW480 and DLD-1 were treated with different concentrations of CB002 at various time points. Cell lines exposed to CB002 showed an increase in p53 target gene expression (i.e. NOXA/DR5/P21) and apoptotic cell death markers (i.e. cleaved caspases and PARP), as early as 16 hrs. Moreover, we showed that CB002 selectively results in apoptotic cell death in cancer cells and not in WI38 normal human lung fibroblast cells as indicated by the Sub-G1 content. To explore the importance of the p53 target genes in apoptotic cell death, we knocked-down DR5 and NOXA proteins. Stable knockdown of NOXA abolished apoptotic cell death whereas DR5 did not, indicating that NOXA is required for CB002-mediated cell death. Following CB002 treatment, we observed an increase in the formation of vacuoles within treated cells. Thus, NOXA induction together with the formation of vacuoles prompted us to investigate if autophagy was playing a role in degradation of mutant p53. Autophagy induction was confirmed by LC3B conversion in cell lysates. CB002 decreased the stability of mutant p53 R175H in HCT116 and RXF393 cells. Although blocking autophagy did not rescue mutant p53 protein expression, induction of autophagy was required for cell death. We further investigated if CB002 was mediating mutant R175H p53 protein degradation through the ubiquitin proteasome system. R175H p53 mutant protein expression was largely rescued by the co-treatment of CB002 with MG132, a proteasomal inhibitor, implicating a role for the ubiquitin proteasome system. Altogether, our data suggests that CB002 stimulates apoptosis through the induction of NOXA and degrades mutant p53 R175H through the ubiquitin proteasome system. In addition, induction of autophagy by CB002 appears to be required for cell death. Hence, our results provide insight into effective p53 pathway activation through the use of
small molecules.
Advisors/Committee Members: Wafik El-Deiry, Thesis Advisor/Co-Advisor, Scot R Kimball, Committee Member, Lisa M Shantz, Committee Member, Rosalyn Bryson Irby, Committee Member.
Subjects/Keywords: mutant p53; apoptosis; autophagy; p53 pathway restoration; small molecules; NOXA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Hernandez Borrero, L. J. (2016). Anti-tumor effect and destabilization of mutant p53 by CB002, a p53-pathway restoring small molecule that stimulates autophagy. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13038ljh216
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Hernandez Borrero, Liz Janice. “Anti-tumor effect and destabilization of mutant p53 by CB002, a p53-pathway restoring small molecule that stimulates autophagy.” 2016. Thesis, Penn State University. Accessed January 20, 2021.
https://submit-etda.libraries.psu.edu/catalog/13038ljh216.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Hernandez Borrero, Liz Janice. “Anti-tumor effect and destabilization of mutant p53 by CB002, a p53-pathway restoring small molecule that stimulates autophagy.” 2016. Web. 20 Jan 2021.
Vancouver:
Hernandez Borrero LJ. Anti-tumor effect and destabilization of mutant p53 by CB002, a p53-pathway restoring small molecule that stimulates autophagy. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Jan 20].
Available from: https://submit-etda.libraries.psu.edu/catalog/13038ljh216.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Hernandez Borrero LJ. Anti-tumor effect and destabilization of mutant p53 by CB002, a p53-pathway restoring small molecule that stimulates autophagy. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/13038ljh216
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Berkeley
19.
Sia, Junren.
Influencing cell fate decisions using physical and chemical cues.
Degree: Bioengineering, 2016, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/0bq39484
► Directed genetic reprogramming of cells from one identity to another offers tremendous potential in regenerative medicine, disease modelling and drug testing. However, its application is…
(more)
▼ Directed genetic reprogramming of cells from one identity to another offers tremendous potential in regenerative medicine, disease modelling and drug testing. However, its application is limited by the low efficiency at which it occurs, and existing methods to improve efficiency mostly utilize additional molecular biology and biochemical manipulations. This thesis explored an alternative paradigm for improving reprogramming efficiency: presentation of physical cues. To this end, I first showed that simply agitating an adherent culture with an orbital shaker enhanced its efficiency of reprogramming to induced pluripotent stem cells (iPSCs). I further demonstrated that convective mixing of the culture medium by orbital agitation blunted the upregulation of CDK inhibitor p57/Kip2 that was caused by the culture becoming overconfluent, which in turn enhanced the efficiency of reprogramming to iPSCs. Next, I showed that culturing reprogramming cells on solid supports scored with microgrooves enhanced their reprogramming into cardiomyocytes. I demonstrated that the microgrooves caused upregulation of the activity of the transcription factor megakaryoblastic leukemia-1 (Mkl1) / myocardin-related transcription factor A (Mrtf-a) and also enhanced organization of sarcomeric structure, with both effects contributing to better reprogramming efficiency. In addition to physical cues, I also explored whether treatment with only small molecules could reprogram fibroblasts into skeletal muscle cells. Indeed, I found that an optimized basal medium (10% FBS in DMEM with 50 μg/ml of ascorbic acid and 50 ng/ml of basic fibroblast growth factor (bFGF)) containing just 2 small molecules— 616452 [an inhibitor of the protein kinase activity of the transforming growth factor-beta (TGF-β) type I receptor (R1)] and forskolin (a plant diterpene that stimulates adenylyl cyclase and elevates the intracellular level of 3',5'-cyclic-AMP)—was sufficient to achieve reprogramming at high efficiency. In summary, this thesis described how both physical and chemical cues can contribute to enhancing the reprogramming of cell identity.
Subjects/Keywords: Biology; Cardiomyocyte; iPSC; Mechanotransduction; Reprogramming; Skeletal muscle; Small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sia, J. (2016). Influencing cell fate decisions using physical and chemical cues. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/0bq39484
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sia, Junren. “Influencing cell fate decisions using physical and chemical cues.” 2016. Thesis, University of California – Berkeley. Accessed January 20, 2021.
http://www.escholarship.org/uc/item/0bq39484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sia, Junren. “Influencing cell fate decisions using physical and chemical cues.” 2016. Web. 20 Jan 2021.
Vancouver:
Sia J. Influencing cell fate decisions using physical and chemical cues. [Internet] [Thesis]. University of California – Berkeley; 2016. [cited 2021 Jan 20].
Available from: http://www.escholarship.org/uc/item/0bq39484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sia J. Influencing cell fate decisions using physical and chemical cues. [Thesis]. University of California – Berkeley; 2016. Available from: http://www.escholarship.org/uc/item/0bq39484
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
20.
Ngom, Mor.
Small molecule stimulators for enhanced yield of human hematopoietic stem cells : Petites molecules stimulatrices pour un rendement accru en cellules souches hématopoietiques humaines.
Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie. Hématologie, 2017, Sorbonne Paris Cité
URL: http://www.theses.fr/2017USPCC320
► Une transduction efficace des cellules souches hematopoïetiques est un préalable pour la thérapie génique des maladies génétiques comme la β‐thalassemie, l’Adrenoleucodystrophie et le Déficit Immunitaire…
(more)
▼ Une transduction efficace des cellules souches hematopoïetiques est un préalable pour la thérapie génique des maladies génétiques comme la β‐thalassemie, l’Adrenoleucodystrophie et le Déficit Immunitaire Combiné Sévère. La petite molécule UM171 à été décrite comme étant une molécule capable de stimuler l’expansion in vitro des cellules souches hématopoïétiques humaines, permettant ainsi une plus large application des thérapies basées sur les cellules souches. Nous avons aussi conduit des études supplémetaires pour confirmer la capacité de UM171 à expandre les souches hématopoïétiques. Durant ce travail, nous avons découvert que UM171 pouvait aussi augmenter de maniére significative, l’efficience de la transduction lentivirale des cellules hématopoïetiques primitives dérivées de sang de cordon. En plus, nous avons montré que UM171 augmentait la transduction des cellules hématopoïeques ayant les phénotypes les plus immatures. Des études plus approfondies ont aussi révélé que UM171 pouvait aussi augmenter la transduction des cellules souches hématopoïétiques avec des lentivirus ayant diffèrent pseudotypes. Au total ces découvertes ont pour conséquence, une nette amélioration des protocoles d’expansion et de transduction des cellules souches hématopoïétiques à travers un meilleur rendement en cellules souches et des taux élevés de transfert de gène en utilisant des quantités réduites de particules virales
Efficient lentiviral gene transfer to hematopoietic stem cells is a prerequisite for theultimate goal of gene therapy for a range of major genetic diseases such as β‐thalassemia, Adrenoleucodystrophy and severe combined immnodeficiency. The small molecule UM171 was recently described as having potent ability to stimulate ex vivo expansion of human hematopoietic stem cells, another key to safer and wider application of stem cell mediated therapies. Here we have conducted additional studies to confirm the stem cell expansion properties of UM171 and in the course of this work discovered that it also has the ability to significantly enhance the efficiency of the lentiviral transduction of primitive hematopietic cells in human cord blood. Subsequent work confirmed that this enhancing effect extends importantly to the most primitive hematopoietic subset as assessed phenotypically and by functional readout in immunodeficient mouse xenografts. Further detailed characterization ofthis phenomenom revealed that UM171’s effects are manifest rapidly and extend to a range of lentiviral pseudotypes. Together these findingsprovide an avenue for improved protocols for hematopoietic stem cell transduction that achieve higher gene efficiency and stem cell recovery coupled with the potential for reduced viral titer requirements.
Advisors/Committee Members: Leboulch, Philippe (thesis director).
Subjects/Keywords: Petite molécule UM171; Vecteurs lentiviraux; Small molecules UM171; Lentiviral vectors
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ngom, M. (2017). Small molecule stimulators for enhanced yield of human hematopoietic stem cells : Petites molecules stimulatrices pour un rendement accru en cellules souches hématopoietiques humaines. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2017USPCC320
Chicago Manual of Style (16th Edition):
Ngom, Mor. “Small molecule stimulators for enhanced yield of human hematopoietic stem cells : Petites molecules stimulatrices pour un rendement accru en cellules souches hématopoietiques humaines.” 2017. Doctoral Dissertation, Sorbonne Paris Cité. Accessed January 20, 2021.
http://www.theses.fr/2017USPCC320.
MLA Handbook (7th Edition):
Ngom, Mor. “Small molecule stimulators for enhanced yield of human hematopoietic stem cells : Petites molecules stimulatrices pour un rendement accru en cellules souches hématopoietiques humaines.” 2017. Web. 20 Jan 2021.
Vancouver:
Ngom M. Small molecule stimulators for enhanced yield of human hematopoietic stem cells : Petites molecules stimulatrices pour un rendement accru en cellules souches hématopoietiques humaines. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2017. [cited 2021 Jan 20].
Available from: http://www.theses.fr/2017USPCC320.
Council of Science Editors:
Ngom M. Small molecule stimulators for enhanced yield of human hematopoietic stem cells : Petites molecules stimulatrices pour un rendement accru en cellules souches hématopoietiques humaines. [Doctoral Dissertation]. Sorbonne Paris Cité; 2017. Available from: http://www.theses.fr/2017USPCC320
Washington State University
21.
[No author].
DEVELOPMENT OF PSMA-TARGETED SPECT IMAGING AGENTS FOR PROSTATE CANCER
.
Degree: 2012, Washington State University
URL: http://hdl.handle.net/2376/4266
► The cell-surface enzyme prostate-specific membrane antigen (PSMA) is up-regulated and strongly expressed on prostate cancer cells associated with high grade primary, androgen independent and metastatic…
(more)
▼ The cell-surface enzyme prostate-specific membrane antigen (PSMA) is up-regulated and strongly expressed on prostate cancer cells associated with high grade primary, androgen independent and metastatic tumors. The ability to target and detect PSMA overexpression in human prostate cancer offers the promise of new avenues of diagnosis and treatment by allowing earlier identification of patients that are at risk for aggressive metastatic disease and provides an opportunity for development of a more personalized course of treatment for patients that would otherwise face poor clinical outcome. ProstaScint (Cytogen) is the only clinically approved PSMA targeted imaging agent for prostate cancer. ProstaScint utilizes an 111In labeled murine antibody for targeted imaging of PSMA. This antibody targets an intracellular epitope of PSMA in primarly non-viable cells and is limited by its slow distribution and clearance. Our lab has developed irreversible phosphoramidate and slowly reversible phosphate inhibitors that also target PSMA with high specificity and affinity. These
small molecule PSMA inhibitors were outfitted chemically with imaging payloads without impacting their binding affinity to PSMA. Our 1st generation PSMA-targeted SPECT agent based on an irreversible PSMA inhibitor core exhibited increasing uptake in the PSMA+ LNCaP cells over time both in vitro and in vivo. More importantly, it was found that it was rapidly internalized into LNCaP cells, presumably through the PSMA enzyme-inhibitor complex. The 2nd generation SPECT imaging agents focused on two objectives: 1) Modular technology for assembly and 2) Evaluating the effects of mode of binding on uptake and internalization. It was found that our 2nd generation SPECT imaging agents based on an irreversible PSMA inhibitor core, exhibited greater uptake and internalization than 2nd generation SPECT imaging agent constructed from a slowly-reversible PSMA inhibitor core. This work demonstrates the successful development of PSMA-targeted SPECT imaging agents using phosphoramidate and phosphate inhibitors modified to deliver 99mTc, a SPECT radionuclide. In addition, our 2nd generation PSMA-targeted SPECT agent demonstrated that it can be assembled efficiently using copper-less click chemistry, supporting a modular approach for the assembly of PSMA-targeted imaging and therapeutic agents.
Advisors/Committee Members: Berkman, Clifford E (advisor).
Subjects/Keywords: Organic chemistry;
Prostate Cancer;
PSMA;
Radio-imaging;
small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
author], [. (2012). DEVELOPMENT OF PSMA-TARGETED SPECT IMAGING AGENTS FOR PROSTATE CANCER
. (Thesis). Washington State University. Retrieved from http://hdl.handle.net/2376/4266
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
author], [No. “DEVELOPMENT OF PSMA-TARGETED SPECT IMAGING AGENTS FOR PROSTATE CANCER
.” 2012. Thesis, Washington State University. Accessed January 20, 2021.
http://hdl.handle.net/2376/4266.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
author], [No. “DEVELOPMENT OF PSMA-TARGETED SPECT IMAGING AGENTS FOR PROSTATE CANCER
.” 2012. Web. 20 Jan 2021.
Vancouver:
author] [. DEVELOPMENT OF PSMA-TARGETED SPECT IMAGING AGENTS FOR PROSTATE CANCER
. [Internet] [Thesis]. Washington State University; 2012. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/2376/4266.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
author] [. DEVELOPMENT OF PSMA-TARGETED SPECT IMAGING AGENTS FOR PROSTATE CANCER
. [Thesis]. Washington State University; 2012. Available from: http://hdl.handle.net/2376/4266
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Vermont
22.
Heaslip, Aoife.
Identification of Small Molecule Effectors of the Toxoplasma.
Degree: PhD, Cell and Molecular Biology, 2008, University of Vermont
URL: https://scholarworks.uvm.edu/graddis/105
► Toxoplasma gondii is an obligate intracellular parasite that can cause lifethreatening disease in immunocompromised individuals. Host cell invasion is therefore central to the pathology of…
(more)
▼ Toxoplasma gondii is an obligate intracellular parasite that can cause lifethreatening disease in immunocompromised individuals. Host cell invasion is therefore central to the pathology of the disease and parasite survival. Unlike many intracellular pathogens, T. gondii does not enter cells by manipulating the host’s phagocytic machinery; instead, the parasite enters the cell by a process of active penetration. Gliding motility and active penetration are driven by a complex of proteins termed the glideosome. The glideosome consists of four major proteins: TgMyoA, an unconventional myosin XIV, myosin light chain (TgMLC1) and glideosome-associated proteins 45 and 50 (TgGAP45, TgGAP50). TgMyoA has been shown to be essential for parasite motility, but the role of TgMLC1 in regulating myosin function remains unknown. Our lab has identified an inhibitor of T. gondii motility and invasion that results in a post-translational modification (PTM) to TgMLC1. Using molecular genetic and mass spectrometry methods we have shown cysteine 53 and cysteine 58 of TgMLC1 are essential for the modification to occur. To determine if the TgMLC1 PTM alters TgMyoA activity, glideosomes were isolated from DMSO- and 115556-treated parasites. Using an in vitro motility assay we have shown that the TgMyoA actin filament displacement velocities are decreased after 115556 treatment. This is the first evidence that TgMLC1 plays a role in regulating TgMyoA activity. The TgMLC1 PTM is responsible, at least in part, for the invasion and motility defects seen in the parasite after compound treatment. During the course of our investigations we have shown that TgMLC1 is dimethylated on lysine 95. This is an unusual modification for cytosolic proteins and has not been previously described for MLCs. Experiments using parasites expressing a non-methylatable form of TgMLC1 (TgMLC1-K95A) show that dimethylation is not necessary for TgMLC1 peripheral localization, TgMLC1 protein-protein interactions and is not required for TgMyoA activity in vitro. However, TgMLC1-K95A does not appear to be phosphoryalted indicating that TgMLC1 dimethylation is necessary for efficient phosphorylation of TgMLC1. These experiments will provide new insight into the ways in which TgMLC1 regulates this unconventional myosin motor complex.
Advisors/Committee Members: Ward, Gary.
Subjects/Keywords: toxoplasma gondii; myosin; small-molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Heaslip, A. (2008). Identification of Small Molecule Effectors of the Toxoplasma. (Doctoral Dissertation). University of Vermont. Retrieved from https://scholarworks.uvm.edu/graddis/105
Chicago Manual of Style (16th Edition):
Heaslip, Aoife. “Identification of Small Molecule Effectors of the Toxoplasma.” 2008. Doctoral Dissertation, University of Vermont. Accessed January 20, 2021.
https://scholarworks.uvm.edu/graddis/105.
MLA Handbook (7th Edition):
Heaslip, Aoife. “Identification of Small Molecule Effectors of the Toxoplasma.” 2008. Web. 20 Jan 2021.
Vancouver:
Heaslip A. Identification of Small Molecule Effectors of the Toxoplasma. [Internet] [Doctoral dissertation]. University of Vermont; 2008. [cited 2021 Jan 20].
Available from: https://scholarworks.uvm.edu/graddis/105.
Council of Science Editors:
Heaslip A. Identification of Small Molecule Effectors of the Toxoplasma. [Doctoral Dissertation]. University of Vermont; 2008. Available from: https://scholarworks.uvm.edu/graddis/105
Harvard University
23.
Garcia-Rivera, Enrique Miguel.
Probing Synovial Sarcomas and the Ubiquitin-Proteasome System With Small Molecules.
Degree: PhD, 2017, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41141313
► Chemical probes have radically transformed our ability to modulate cellular activity by providing robust and reversible disruption of select biological processes. To uncover a novel…
(more)
▼ Chemical probes have radically transformed our ability to modulate cellular activity by providing robust and reversible disruption of select biological processes. To uncover a novel set of these tools, I first performed a small molecule screen to identify compounds that could selectively prevent the growth of synovial sarcoma (SS) cell lines and observed that MET inhibitors could target a distinct subset. This MET sensitivity was defined by amplification of the MET gene and an active AKT pathway. Through immunohistochemistry of SS patient tumor samples, I discovered that MET is only expressed in the glandular component of biphasic SS, the same histological subtype of the SS cell lines that were sensitive to MET inhibition. Furthermore, this dependency could be targeted in vivo, with the MET inhibitor SGX-523 preventing the growth of a biphasic SS xenograft in mice. I also compared the transcriptional changes caused by MET inhibition to loss of SS18-SSX1, the fusion protein understood to initiate SS oncogenesis. These two perturbations were found to behave very similarly, altering pathways associated to the epithelial to mesenchymal transition, cell-cycle progression, and differentiation. This is one of the first targetable dependencies discovered in this cancer and it could have a marked impact in the future of SS treatment.
Second I executed a screen to identify compounds that could increase the protein levels of the tumor suppressor BAF47 in SS cells and discovered BRD1732, a novel probe of the ubiquitin-proteasome pathway with a novel mechanism of action (MOA) and a yet to be identified target. Cellular treatment with BRD1732 causes a profound increase in the levels of free cellular ubiquitin alongside various protein level increases (e.g. of p21/p27), inhibition of NFκB signaling, and inhibition of the unfolded protein response. The compound does not inhibit the human 26S proteasome, E1 or most E2 enzymes in vitro, suggesting a unique MOA distinct from canonical proteasome inhibition. BRD1732 can also prevent the growth of various cancer cell lines, indicating a potential for translation into the clinic. This probe could uncover novel biology surrounding protein homeostasis and further the therapeutic relevance of the ubiquitin-proteasome pathway.
Medical Sciences
Advisors/Committee Members: Kadoch, Cigall (advisor), Hanna, John (committee member), Ploegh, Hidde (committee member), Calo, Eliezer (committee member).
Subjects/Keywords: small molecules; synovial sarcomas; MET; ubiquitin; proteasome; inhibitors; chemical probes
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Garcia-Rivera, E. M. (2017). Probing Synovial Sarcomas and the Ubiquitin-Proteasome System With Small Molecules. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:41141313
Chicago Manual of Style (16th Edition):
Garcia-Rivera, Enrique Miguel. “Probing Synovial Sarcomas and the Ubiquitin-Proteasome System With Small Molecules.” 2017. Doctoral Dissertation, Harvard University. Accessed January 20, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41141313.
MLA Handbook (7th Edition):
Garcia-Rivera, Enrique Miguel. “Probing Synovial Sarcomas and the Ubiquitin-Proteasome System With Small Molecules.” 2017. Web. 20 Jan 2021.
Vancouver:
Garcia-Rivera EM. Probing Synovial Sarcomas and the Ubiquitin-Proteasome System With Small Molecules. [Internet] [Doctoral dissertation]. Harvard University; 2017. [cited 2021 Jan 20].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41141313.
Council of Science Editors:
Garcia-Rivera EM. Probing Synovial Sarcomas and the Ubiquitin-Proteasome System With Small Molecules. [Doctoral Dissertation]. Harvard University; 2017. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41141313
Harvard University
24.
Shaw, Katharin.
A Chemical Biology Platform to Develop Small Molecule Probes for Bromodomains.
Degree: PhD, 2017, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41142078
► Bromodomain epigenetic reader proteins play crucial roles in the pathogenesis of diseases ranging from inflammation to cancer. Small molecule inihibitors have engendered a nuanced understanding…
(more)
▼ Bromodomain epigenetic reader proteins play crucial roles in the pathogenesis of diseases ranging from inflammation to cancer. Small molecule inihibitors have engendered a nuanced understanding of the role of BET subfamily bromodomains in multiple diseases. Here, platforms were established to facilitate chemical probe development for the remaining ~50 bromodomains with a concentrated focus on establishing a pipeline for the discovery of CBP bromodomain inhibitors.
CBP is a large bromodomain-containing transcriptional co-activator involved in cell proliferation and growth, cellular differentiation and development, cognitive function, and cell adhesion. It is involved in the pathogenesis of cancer, in particular hematologic diseases. A high-throughput biochemical assay, cellular viability assay, and cellular target engagement assay were established in order to screen and validate small molecule inhibitors of the CBP bromodomain. A family-wide bromodomain profiling platform (BROMOscan) was established and fully validated to provide broad quantitative binding affinity and selectivity information. Using this platform, novel small molecule inhibitors for non-BET domains were discovered. Moreover, a LRRK2 kinase inhibitor with potent bromodomain cross-reactivity was identified and optimized. Using BROMOscan and the CBP bromodomain assays deeloped here, a dually functioning kinase-bromodomain inhibitor was discovered that was potent and selective for CBP.
Chemical Biology
Advisors/Committee Members: Bradner, James (advisor), Clardy, Jon (committee member), Gray, Nathanael S. (committee member).
Subjects/Keywords: chemical biology; assay development; bromodomains; epigenetics; inhibition; small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Shaw, K. (2017). A Chemical Biology Platform to Develop Small Molecule Probes for Bromodomains. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:41142078
Chicago Manual of Style (16th Edition):
Shaw, Katharin. “A Chemical Biology Platform to Develop Small Molecule Probes for Bromodomains.” 2017. Doctoral Dissertation, Harvard University. Accessed January 20, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:41142078.
MLA Handbook (7th Edition):
Shaw, Katharin. “A Chemical Biology Platform to Develop Small Molecule Probes for Bromodomains.” 2017. Web. 20 Jan 2021.
Vancouver:
Shaw K. A Chemical Biology Platform to Develop Small Molecule Probes for Bromodomains. [Internet] [Doctoral dissertation]. Harvard University; 2017. [cited 2021 Jan 20].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41142078.
Council of Science Editors:
Shaw K. A Chemical Biology Platform to Develop Small Molecule Probes for Bromodomains. [Doctoral Dissertation]. Harvard University; 2017. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:41142078
Eastern Michigan University
25.
Weerakoon, Darshani Avanthi.
Design, synthesis and evaluation of small molecules as inhibitors of plasminogen activator inhibitor-1.
Degree: MS, Chemistry, 2014, Eastern Michigan University
URL: https://commons.emich.edu/theses/705
► Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. Excessive levels of PAI-1 inhibit urokinase-type plasminogen activator (uPA)…
(more)
▼ Plasminogen activator inhibitor type-1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. Excessive levels of PAI-1 inhibit urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), which regulates fibrinolysis as well as the development of different pathological diseases like obesity, metabolic syndrome, tumor invasion and metastasis, and coronary heart disease. Currently, there is no Food and Drug Administration approval for inactivating higher levels of PAI-1. Therefore, PAI-1 is considered an attractive drug target. Due to PAI-1’s different structural conformations and multiple binding domains, development of PAI-1 inhibitors is a challenging situation. In this research study, we describe the synthesis and evaluation of novel low molecular weight amides containing various moieties, including para-chlorobenzyl, polyphenol, oxindole, or isatin-based units. By changing the architectural scheme of these compounds we hope to effectively change the potency of our inhibitors, and will be able to develop a structure-activity relationship that will allow us to design a more potent
small molecule as a PAI-1 inhibitor. Therefore, the synthesis and structure-activity relationship of those novel
small molecules are discussed in this paper.
Advisors/Committee Members: Cory D. Emal, PhD, Chair, Gregg Wilmes, PhD, Ingo Janser, PhD.
Subjects/Keywords: Drug design; Drug synthesis; Isatin; Oxindole; PAI-1; Small molecules; Chemistry
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Weerakoon, D. A. (2014). Design, synthesis and evaluation of small molecules as inhibitors of plasminogen activator inhibitor-1. (Masters Thesis). Eastern Michigan University. Retrieved from https://commons.emich.edu/theses/705
Chicago Manual of Style (16th Edition):
Weerakoon, Darshani Avanthi. “Design, synthesis and evaluation of small molecules as inhibitors of plasminogen activator inhibitor-1.” 2014. Masters Thesis, Eastern Michigan University. Accessed January 20, 2021.
https://commons.emich.edu/theses/705.
MLA Handbook (7th Edition):
Weerakoon, Darshani Avanthi. “Design, synthesis and evaluation of small molecules as inhibitors of plasminogen activator inhibitor-1.” 2014. Web. 20 Jan 2021.
Vancouver:
Weerakoon DA. Design, synthesis and evaluation of small molecules as inhibitors of plasminogen activator inhibitor-1. [Internet] [Masters thesis]. Eastern Michigan University; 2014. [cited 2021 Jan 20].
Available from: https://commons.emich.edu/theses/705.
Council of Science Editors:
Weerakoon DA. Design, synthesis and evaluation of small molecules as inhibitors of plasminogen activator inhibitor-1. [Masters Thesis]. Eastern Michigan University; 2014. Available from: https://commons.emich.edu/theses/705
University of California – Berkeley
26.
Soto, Jennifer.
Biochemical and Biophysical Regulation of Cell Reprogramming.
Degree: Bioengineering, 2016, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/81n7s6pv
► Cell reprogramming, the reverse process of differentiation, represents a major advancement in cell biology and has wide applications in regenerative medicine, drug screening and disease…
(more)
▼ Cell reprogramming, the reverse process of differentiation, represents a major advancement in cell biology and has wide applications in regenerative medicine, drug screening and disease modeling. Induced pluripotent stem cell (iPSC) reprogramming and direct conversion are two promising approaches to manipulate cell fate. Although extensive studies have been conducted on the role of chemical methods and biomaterials in iPSC reprogramming, their effect on direct reprogramming, the process of converting a somatic cell into a distantly related cell type while avoiding a pluripotent state, have not been fully explored. In this dissertation, we demonstrate, for the first time, that small molecules that disrupt the cytoskeleton, more specifically inhibitors of cell contractility, can significantly improve the direct reprogramming of adult fibroblasts into neurons by modulating gene and protein expression. Furthermore, our findings suggest that focal adhesions and the nuclear lamina play a critical role in this direct reprogramming process. In addition to soluble chemical factors from the microenvironment, the physical microenvironment can also strongly influence cellular processes. Thus, we investigated how biophysical factors regulated induced neuronal conversion. We explored the effects of topography on this process, utilizing poly(dimethylsiloxane) (PDMS) microgrooves and electrospun nanofibrous membranes as our bioengineered substrates in conjunction with lentiviral delivery of specific neurogenic transcription factors. We unraveled that nanoscale cues, in comparison to microscale cues, were more effective at promoting induced neuronal reprogramming. The derivation of induced neuronal cells using direct reprogramming not only serves to provide a platform for neurological disease modeling but moreover, holds great promise for personalized medicine as the generation of patient-specific cells can be valuable for drug discovery and the development of new therapeutics.
Subjects/Keywords: Biomedical engineering; cell reprogramming; cytoskeleton; direct conversion; microgrooves; nanofibers; small molecules
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Soto, J. (2016). Biochemical and Biophysical Regulation of Cell Reprogramming. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/81n7s6pv
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Soto, Jennifer. “Biochemical and Biophysical Regulation of Cell Reprogramming.” 2016. Thesis, University of California – Berkeley. Accessed January 20, 2021.
http://www.escholarship.org/uc/item/81n7s6pv.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Soto, Jennifer. “Biochemical and Biophysical Regulation of Cell Reprogramming.” 2016. Web. 20 Jan 2021.
Vancouver:
Soto J. Biochemical and Biophysical Regulation of Cell Reprogramming. [Internet] [Thesis]. University of California – Berkeley; 2016. [cited 2021 Jan 20].
Available from: http://www.escholarship.org/uc/item/81n7s6pv.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Soto J. Biochemical and Biophysical Regulation of Cell Reprogramming. [Thesis]. University of California – Berkeley; 2016. Available from: http://www.escholarship.org/uc/item/81n7s6pv
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
National University of Ireland – Galway
27.
Negi, Arvind.
Investigation of various ligand design approaches and synthesis of diverse heterocyclic bioactive compounds
.
Degree: 2019, National University of Ireland – Galway
URL: http://hdl.handle.net/10379/15468
► Structure-based design and ligand-based design are one of the most common approaches used to develop new inhibitors against druggable protein targets in various human disorders.…
(more)
▼ Structure-based design and ligand-based design are one of the most common approaches used to develop new inhibitors against druggable protein targets in various human disorders. Mcl-1 is a protein belongs to Bcl-2 family which has a prime role in apoptosis and therefore its targeting improvises its mitogenic effect in a number of serious complications such as neurodegenerative disorders and cancers. However, various heterocyclic cores were used to developed Mcl-1 inhibitors in last few decades (mainly, polyphenols, thiazoles, thiazolo[3,2-a]pyrimidinone, indoles, acenaphthylene-phenalenes, pyrroles, isoquinoline-quinolines, anthraquinone-quinazolines, naphthols, salicylic-anthranilic acids, benzylpiperazines, pyrazolo[1,5-a]pyridines, isoindolines, imidazolidine-2,4-dione, non-peptidomimetic macrocycles), and is compiled in objective 2.1 of chapter 2 of this thesis. Also, various naturally-derived compounds (such as gymnochrome-F, oxy-polyhalogenated diphenyl ethers, anacardic acids, endiandric acids, marinopyrroles cryptosphaerolide, meiogynins) were also discovered in the past and had shown low micromolar activity against Mcl-1. However, lack of their biophysical studies leads to objective 2.2 of chapter 2 where the concept of multiple-receptor conformation and multiple-ligand conformation was used initially to evaluate the employed methodology, used for finding the precise and accurate docking structures of these naturally derived Mcl-1 inhibitors. Finally, the resulted dock scores of respective naturally derived Mcl-1 inhibitors were compared with their Mcl-1 binding affinities. The previous ligand design information clearly indicates simple structures such as diphenyl propenone structures could be beneficial in tight binding to P2-P3 or P3-P4 pocket of Mcl-1 protein. Based on parent structure binding, further exploration of these structures were performed to enhance the scope of the structure-activity relationship (such as synthesis of pyrazolines, pyrazoles, O-phenyl alkyl bromides, N-substituted pyrazoles, 5-amino-4-cyano-diphenyl pyridines, symmetrical and asymmetrical triphenyl pyridines, imidazoles and indoles). However, a novel synthetic method was also developed to improve the yield and scope of triphenyl pyridines.
Chapter 3 involves the designing and synthesis of non-peptidomimetic secondary protein structures as alpha-helix or as beta-sheets where Objective 3.1 contains synthesis of Bis-triphenyl pyridine core and Triphenyl pyridine-pyrazole core as BH3 alpha helix. This is the first time that a Bis-triphenyl core and triphenyl pyridine pyrazole core is reported. However, the second objective (objective 3.2) provides a computational study of macrocycle-embedded carbohydrates for serotonin isoforms and ions channels (Negi et al., Eur J Med
Chem, 2019, 176, 292-309). The highlights of this study were the construction of the homology models of NK2, 5HT1A, 5HT2A Site-2 of the sodium channel and retro screening of in-house compounds.
In chapter 4, special focus was given on the biophysical studies of…
Advisors/Committee Members: Murphy, Paul (advisor).
Subjects/Keywords: Drug design;
Synthesis;
Small molecules;
Apoptosis;
Chemistry;
Science
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Negi, A. (2019). Investigation of various ligand design approaches and synthesis of diverse heterocyclic bioactive compounds
. (Thesis). National University of Ireland – Galway. Retrieved from http://hdl.handle.net/10379/15468
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Negi, Arvind. “Investigation of various ligand design approaches and synthesis of diverse heterocyclic bioactive compounds
.” 2019. Thesis, National University of Ireland – Galway. Accessed January 20, 2021.
http://hdl.handle.net/10379/15468.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Negi, Arvind. “Investigation of various ligand design approaches and synthesis of diverse heterocyclic bioactive compounds
.” 2019. Web. 20 Jan 2021.
Vancouver:
Negi A. Investigation of various ligand design approaches and synthesis of diverse heterocyclic bioactive compounds
. [Internet] [Thesis]. National University of Ireland – Galway; 2019. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/10379/15468.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Negi A. Investigation of various ligand design approaches and synthesis of diverse heterocyclic bioactive compounds
. [Thesis]. National University of Ireland – Galway; 2019. Available from: http://hdl.handle.net/10379/15468
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Oregon
28.
Coonrod, Leslie.
Targeting Myotonic Dystrophy with Small Molecules.
Degree: 2012, University of Oregon
URL: http://hdl.handle.net/1794/12379
► Myotonic dystrophy (DM) is one of the most common forms of muscular dystrophy, characterized by its hallmark symptom myotonia. DM is an autosomal dominant disease…
(more)
▼ Myotonic dystrophy (DM) is one of the most common forms of muscular dystrophy, characterized by its hallmark symptom myotonia. DM is an autosomal dominant disease caused by a toxic gain of function RNA. The toxic RNA is produced from expanded non-coding CTG/CCTG repeats, and these CUG/CCUG repeats sequester a family of RNA binding proteins. The Muscleblind-like (MBNL) family of RNA binding proteins are sequestered to the expanded CUG/CCUG repeats. The MBNL proteins are regulators of alternative splicing, and their sequestration to the toxic RNA leads to mis-splicing events, which are believed to cause the symptoms observed in DM patients.
A previously reported screen for
small molecules used to identify compounds that could disrupt MBNL from binding the toxic CUG repeats found that pentamidine was able to rescue splicing defects associated with DM. Herein, we present a new class of
molecules (phenolsulphonphthaleins) that inhibited MBNL1/CUG repeat complex formation in a competitive electrophoretic mobility shift assay (EMSA). Additionally, one of these
molecules, bromophenol blue (BPB), acted in a synergistic manner with the previously described inhibitor pentamidine. We also demonstrated that the halogenation of the phenolsulphonphthalein dyes is an important factor for activity. Moreover, we presentant analysis of a series of methylene linker variants of pentamidine that revealed heptamidine (an analog of pentamidine) could reverse splicing defects in a DM1 tissue culture model and rescue myotonia in a DM1 mouse model.
Finally, we report on a new crystal structure of CUG repeats, crystallized in the context of a GAAA tetraloop/receptor which facilitated ordered packing within the crystal. This structure was consistent with previous structures showing that the repeats are essentially A-form RNA, despite having a U-U mismatch every third base pair. We also identified six types of U-U mismatch in the context of the 5'CUG/3'GUC motif, suggesting that the interactions between the uridines are dynamic. This structure also contains the highest resolution GAAA tetraloop/receptor structure (1.95 Å) reported to date.
This dissertation includes previously unpublished co-authored material.
Advisors/Committee Members: Berglund, J. Andrew (advisor).
Subjects/Keywords: CUG repeats; Myotonic dystrophy; RNA structure; Small molecules; Toxic RNA
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Coonrod, L. (2012). Targeting Myotonic Dystrophy with Small Molecules. (Thesis). University of Oregon. Retrieved from http://hdl.handle.net/1794/12379
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Coonrod, Leslie. “Targeting Myotonic Dystrophy with Small Molecules.” 2012. Thesis, University of Oregon. Accessed January 20, 2021.
http://hdl.handle.net/1794/12379.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Coonrod, Leslie. “Targeting Myotonic Dystrophy with Small Molecules.” 2012. Web. 20 Jan 2021.
Vancouver:
Coonrod L. Targeting Myotonic Dystrophy with Small Molecules. [Internet] [Thesis]. University of Oregon; 2012. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1794/12379.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Coonrod L. Targeting Myotonic Dystrophy with Small Molecules. [Thesis]. University of Oregon; 2012. Available from: http://hdl.handle.net/1794/12379
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of Toronto
29.
Goodreid, Jordan D.
Synthesis and Biological Evaluation of Antibacterial Small Molecule Activators of Caseinolytic Protease P and the Synthetic Utility of Metal Carboxylate Salts in Amidation Reactions with Amines.
Degree: PhD, 2016, University of Toronto
URL: http://hdl.handle.net/1807/76441
► This thesis is presented in two parts and summarizes work carried out in the laboratory of Professor Robert A. Batey at the University of Toronto…
(more)
▼ This thesis is presented in two parts and summarizes work carried out in the laboratory of Professor Robert A. Batey at the University of Toronto from September 2009 through March 2016. Part 1 of this thesis covers the synthesis and biological evaluation of two types of
small molecules which target bacterial Caseinolytic Protease P (ClpP); these are the cyclic acyldepsipeptide (ADEP) class of antibiotics and related analogues (Chapter 2) and the ACP1 analogues (Chapter 3). Part 2 of this thesis outlines work related to the synthetic utility of metal carboxylate salts in amide bond-forming reactions with amines.
Part 1 of this thesis begins with an introductory chapter (Chapter 1) on antibiotics to familiarize the reader with antibiotic classes, bacterial mechanisms of drug resistance as well as strategies for antibacterial drug discovery. Next, Chapter 2 details the total synthesis and biological evaluation of the A54556 ADEP natural products and related analogues. In the course of our investigations on this class of compound, a rapid two-step synthetic approach was developed that utilized a combination of solid-phase peptide chemistry and a novel lanthanide salt-promoted macrolactonization reaction. Importantly, this methodology was used to prepare several structurally diverse analogues. Chapter 3 then describes the synthesis and biological evaluation of ACP1 and related analogues. In contrast to the ADEPs, ACP1 was discovered using a high-throughput screen and several structurally unique analogues were synthesized in an attempt to improve potency and understand the structural features that impart biological activity.
Part 2 of this thesis covers amidation reactions from the direct coupling of metal carboxylate salts with amines or ammonium salts in the presence of the coupling reagent HBTU (Chapter 4). A wide variety of carboxylate salts were examined and the methodology was later extended to multistep, one-pot variants using carboxylate salts that were generated in situ.
Advisors/Committee Members: Batey, Robert A, Chemistry.
Subjects/Keywords: Amidation; Antibacterial; Carboxylate Salts; Depsipeptides; Small Molecules; Synthesis; 0490
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Goodreid, J. D. (2016). Synthesis and Biological Evaluation of Antibacterial Small Molecule Activators of Caseinolytic Protease P and the Synthetic Utility of Metal Carboxylate Salts in Amidation Reactions with Amines. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/76441
Chicago Manual of Style (16th Edition):
Goodreid, Jordan D. “Synthesis and Biological Evaluation of Antibacterial Small Molecule Activators of Caseinolytic Protease P and the Synthetic Utility of Metal Carboxylate Salts in Amidation Reactions with Amines.” 2016. Doctoral Dissertation, University of Toronto. Accessed January 20, 2021.
http://hdl.handle.net/1807/76441.
MLA Handbook (7th Edition):
Goodreid, Jordan D. “Synthesis and Biological Evaluation of Antibacterial Small Molecule Activators of Caseinolytic Protease P and the Synthetic Utility of Metal Carboxylate Salts in Amidation Reactions with Amines.” 2016. Web. 20 Jan 2021.
Vancouver:
Goodreid JD. Synthesis and Biological Evaluation of Antibacterial Small Molecule Activators of Caseinolytic Protease P and the Synthetic Utility of Metal Carboxylate Salts in Amidation Reactions with Amines. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1807/76441.
Council of Science Editors:
Goodreid JD. Synthesis and Biological Evaluation of Antibacterial Small Molecule Activators of Caseinolytic Protease P and the Synthetic Utility of Metal Carboxylate Salts in Amidation Reactions with Amines. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/76441
University of Toronto
30.
Cheng, Xinran.
Development of Biosensors to Monitor the Interaction of Small Molecules with Amyloidogenic Proteins using Optical and Electrochemical Methods.
Degree: PhD, 2015, University of Toronto
URL: http://hdl.handle.net/1807/69263
► Amyloidogenic protein fibrils are well known pathological hallmark of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The Amyloid Cascade Hypothesis attributes…
(more)
▼ Amyloidogenic protein fibrils are well known pathological hallmark of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The Amyloid Cascade Hypothesis attributes the onset and progression of AD to an imbalance in amyloid-beta (Abeta). In PD, a definitive diagnosis of Parkinson's disease can be confirmed only by post mortem examination of the patient's substantia nigra for the presence of Lewy bodies, mainly comprised of alpha-synuclein (a-S). As the toxicity in these neurodegenerative diseases is highly correlated with the formation of soluble oligomers from their corresponding proteins, a strategy to inhibit the aggregation of Abeta and a-S may help to ameliorate AD and PD respectively (Chapter 1). Herein, we review the fundamentals of electrochemistry (Chapter 2) before demonstrating the use of electrochemical techniques, acoustic wave sensor and BiacoreX surface plasmon resonance (SPR) to characterize the aggregation of Abeta (Chapter 3). We have shown that amyloid aggregation could be monitored through these label-free methods and clioquinol (CQ) inhibits the progression of aggregation. We further increased the throughput of monitored
small molecules and Abeta interactions through the use of SPR imaging (SPRi) (Chapter 4) and LED-interferometric reflective imaging sensor (LED-IRIS) (Chapter 5). These studies showed that epigallocatechin gallate (EGCG) modulates the Abeta aggregation pathway to form beta-sheet absent aggregates while certain metal ions generally accelerate the Abeta aggregation process to form thick mature fibrils. These results are supported by Thioflavin T (ThT) and transmission electron microscopy (TEM) studies.We then studied the effects of CQ on a-S (Chapter 6) using electrochemical techniques and spectroscopic dyes such as ThT and Congo Red. Both electrochemical and spectroscopic studies showed that Cu(II) accelerated the fibril formation of a-S, while CQ inhibited such activity. This electrochemical analysis was further modified to include an optical screening test on the same transduction platform by utilizing nanosphere lithography (NSL) (Chapter 7). Complemented by Localized-SPR, SPRi, TEM and ThT studies, it was found that dense and unstructured amorphous a-S aggregates were induced by EGCG, while beta-sheet-rich and compact a-S mesh-networks were promoted by Cu(II) ions, in agreement with previous results.
Advisors/Committee Members: Kerman, Kagan, Chemistry.
Subjects/Keywords: aggregation; amyloid; biosensor; electrochemistry; optical; small molecules; 0485
Record Details
Similar Records
Cite
Share »
Record Details
Similar Records
Cite
« Share
❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cheng, X. (2015). Development of Biosensors to Monitor the Interaction of Small Molecules with Amyloidogenic Proteins using Optical and Electrochemical Methods. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/69263
Chicago Manual of Style (16th Edition):
Cheng, Xinran. “Development of Biosensors to Monitor the Interaction of Small Molecules with Amyloidogenic Proteins using Optical and Electrochemical Methods.” 2015. Doctoral Dissertation, University of Toronto. Accessed January 20, 2021.
http://hdl.handle.net/1807/69263.
MLA Handbook (7th Edition):
Cheng, Xinran. “Development of Biosensors to Monitor the Interaction of Small Molecules with Amyloidogenic Proteins using Optical and Electrochemical Methods.” 2015. Web. 20 Jan 2021.
Vancouver:
Cheng X. Development of Biosensors to Monitor the Interaction of Small Molecules with Amyloidogenic Proteins using Optical and Electrochemical Methods. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Jan 20].
Available from: http://hdl.handle.net/1807/69263.
Council of Science Editors:
Cheng X. Development of Biosensors to Monitor the Interaction of Small Molecules with Amyloidogenic Proteins using Optical and Electrochemical Methods. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/69263
◁ [1] [2] [3] [4] [5] [6] [7] ▶
. 
Open Access Theses and Dissertations
