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You searched for +publisher:"Georgia Tech" +contributor:("Donald Doyle"). Showing records 1 – 3 of 3 total matches.

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Georgia Tech

1. Urs, Aarti N. Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17.

Degree: MS, Biology, 2005, Georgia Tech

Steroidogenic factor (SF1) is an orphan nuclear receptor that is essential for steroid hormone-biosynthesis and endocrine development. Recent studies have demonstrated that phospholipids are ligands for SF1. In the present study our aim was to identify endogenous ligands for SF1 and characterize their functional significance in mediating cAMP-dependent transcription of human CYP17. Using mass spectrometry we show that in H295R adrenocortical cells SF1 is bound to sphingosine (SPH) under basal conditions and that cAMP stimulation decreases the amount of SPH bound to the receptor. We also show that silencing both acid and neutral ceramidases using siRNA induces CYP17 mRNA expression, suggesting that SPH acts as an inhibitory ligand. In vitro analysis of ligand binding using scintillation proximity assays show that several sphingolipids and phospholipids, including phosphatidic acid (PA), can compete with [3H]SPH for binding to SF1, suggesting that SF1 may have more than one ligand and binding specificity may change with the changes in intracellular fluxes of phospholipids. Further, phosphatidic acid (PA) induces SF1-dependent transcription of CYP17 reporter constructs. Inhibition of diacyglycerol kinase (DAGK) activity using R59949 and silencing DAGK- expression attenuates SF1-dependent CYP17 transcriptional. We propose that PA is an activating ligand for SF1 and that cAMP-stimulated activation of SF1 takes place by displacement of SPH. Advisors/Committee Members: Marion Sewer (Committee Chair), Alfred Merrill (Committee Member), Donald Doyle (Committee Member), Harish Radhakrishna (Committee Member).

Subjects/Keywords: CYP17; Sphingosine; Phosphatidic acids; Steroidogenic factor 1; Transcription factors; Steroid hormones Synthesis; Sphingosine; Pregnenolone; Phospholipids; Ligands

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APA (6th Edition):

Urs, A. N. (2005). Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7638

Chicago Manual of Style (16th Edition):

Urs, Aarti N. “Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17.” 2005. Masters Thesis, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/7638.

MLA Handbook (7th Edition):

Urs, Aarti N. “Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17.” 2005. Web. 23 Jan 2021.

Vancouver:

Urs AN. Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17. [Internet] [Masters thesis]. Georgia Tech; 2005. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/7638.

Council of Science Editors:

Urs AN. Reciprocal binding of sphingosine and phosphatidic acid to steroidogenic factor 1 regulates the transcription of CYP17. [Masters Thesis]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7638


Georgia Tech

2. Gotz, Marion Gabriele. Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases.

Degree: PhD, Chemistry and Biochemistry, 2004, Georgia Tech

Cysteine proteases are a class of proteolytic enzymes, which are involved in a series of metabolic and catabolic processes, such as protein turnover, digestion, blood coagulation, apoptosis, fertilization and cell differentiation, and the immune response system. The development of novel potent and selective inhibitors for cysteine proteases has therefore gained increasing attention among medicinal chemists. In this thesis we have reported the design, synthesis, and evaluation of several peptidyl inhibitors for clan CA and clan CD cysteine proteases. We have continued the investigation of dipeptidyl vinyl sulfones as potent and selective inhibitors for dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease, which is involved in the processing of intracellular proteases, such as granzymes. We have found that DPPI tolerates negatively charged amino acid residues in the P2 position with inhibition rates of 7,600 M-1s-1. Dipeptidyl vinyl sulfones with positively charged amino acid residues at the P1 position, however, do not inhibit DPPI at all. A second project focused on the epoxidation of the double bond of the vinyl sulfone moiety of the dipeptidyl vinyl sulfones. Instead of epoxidizing the double bond, we found that an isomerization had occurred. The newly formed compounds were determined to be allyl sulfones. We tested this new class of inhibitors with clan CA proteases and obtained inhibition rates of 560 M-1s-1 for Cbz-Leu-Phe-AS-Ph with calpain I. Two new classes of compounds for the clan CD protease S. mansoni legumain were designed, synthesized, and evaluated. Aza-peptidyl epoxides were found to be potent and selective inhibitors of S. mansoni legumain with IC50’s as low as 45 nM. Aza-peptide Michael acceptors were derived from the aza-peptide epoxide design and synthesized in an analogous fashion. The aza-peptide Michael acceptors inhibited S. mansoni legumain with even lower IC50’s, as low as 10 nM. However, the aza-peptide Michael acceptors react with thioalkylating agents contained in the buffer, such as DTT. The rates of degradation were determined spectroscopically, and half-lives of 3 to 20 minutes were measured. This observation gave us insights into the enzymatic mechanism and allowed us to determine the point of attack for the legumain active site cysteine thiol. Advisors/Committee Members: Dr. James C. Powers (Committee Chair), Dr. Donald Doyle, Dr. Nicholas Hud, Dr. Niren Murthy, and Dr. Suzanne Shuker (Committee Members).

Subjects/Keywords: Allyl sulfone; Aza-peptide; Biosynthesis; Cysteine protease; Cysteine proteinases; Irreversible inhibitors; Protease inhibitors; Sulphones; Vinyl sulfone

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APA (6th Edition):

Gotz, M. G. (2004). Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/8072

Chicago Manual of Style (16th Edition):

Gotz, Marion Gabriele. “Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases.” 2004. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/8072.

MLA Handbook (7th Edition):

Gotz, Marion Gabriele. “Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases.” 2004. Web. 23 Jan 2021.

Vancouver:

Gotz MG. Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases. [Internet] [Doctoral dissertation]. Georgia Tech; 2004. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/8072.

Council of Science Editors:

Gotz MG. Design, synthesis, and evaluation of irreversible peptidyl inhibitors for clan CA and clan CD cysteine proteases. [Doctoral Dissertation]. Georgia Tech; 2004. Available from: http://hdl.handle.net/1853/8072


Georgia Tech

3. Roberts, Lezah Wilette. Effect of Netropsin on One-electron Oxidation of DNA.

Degree: PhD, Chemistry and Biochemistry, 2005, Georgia Tech

One electron oxidation of DNA has been studied extensively over the years. When a charge is injected into a DNA duplex, it migrates through the DNA until it reaches a trap. Upon further reactions, damage occurs in this area and strand cleavage can occur. Many works have been performed to see what can affect this damage to DNA. Netropsin is a minor groove binder that can bind to tracts of four to five A:T base pairs. It has been used in the studies within to determine if it can protect DNA against oxidative damage, caused by one-electron oxidation, when it is bound within the minor groove of the DNA. By using a naphthacenedione derivative as a photosensitizer, several DNA duplexes containing netropsin binding sites as well as those without binding sites, were irradiated at 420 nm, analyzed, and visualized to determine its effect on oxidative damage. It has been determined netropsin creates a quenching sphere of an average of 5.8 * 108 Šwhether bound to the DNA or not. Herein we will show netropsin protects DNA against oxidative damage whether it is free in solutions or bound within the minor groove of a DNA duplex. Advisors/Committee Members: Gary B. Schuster (Committee Chair), Donald Doyle (Committee Member), Laren Tolbert (Committee Member), Nicholas V. Hud (Committee Member), Roger Wartell (Committee Member).

Subjects/Keywords: Photosensitizer; Charge transfer; Netropsin; TQ; DNA; Electron transfer; One-electron oxidation; Photosensitization, Biological; Charge transfer in biology; DNA Analysis; Oxidation, Physiological

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Roberts, L. W. (2005). Effect of Netropsin on One-electron Oxidation of DNA. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/7228

Chicago Manual of Style (16th Edition):

Roberts, Lezah Wilette. “Effect of Netropsin on One-electron Oxidation of DNA.” 2005. Doctoral Dissertation, Georgia Tech. Accessed January 23, 2021. http://hdl.handle.net/1853/7228.

MLA Handbook (7th Edition):

Roberts, Lezah Wilette. “Effect of Netropsin on One-electron Oxidation of DNA.” 2005. Web. 23 Jan 2021.

Vancouver:

Roberts LW. Effect of Netropsin on One-electron Oxidation of DNA. [Internet] [Doctoral dissertation]. Georgia Tech; 2005. [cited 2021 Jan 23]. Available from: http://hdl.handle.net/1853/7228.

Council of Science Editors:

Roberts LW. Effect of Netropsin on One-electron Oxidation of DNA. [Doctoral Dissertation]. Georgia Tech; 2005. Available from: http://hdl.handle.net/1853/7228

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