subject:(T brucei)

University of Edinburgh

1. McDonald, Lindsay Mary. Ordering components of the slender to stumpy signalling pathway in Trypanosoma brucei.

Degree: PhD, 2016, University of Edinburgh

URL: http://hdl.handle.net/1842/19573

► In the mammalian bloodstream, the protozoan parasite Trypanosoma brucei undergoes differentiation from proliferative slender forms to arrested, transmissible, stumpy forms. This transition is associated with… (more)

▼ In the mammalian bloodstream, the protozoan parasite Trypanosoma brucei undergoes differentiation from proliferative slender forms to arrested, transmissible, stumpy forms. This transition is associated with extensive cytological and metabolic changes that promote survival in the tsetse midgut, and also influences infection dynamics within the mammalian host. A number of genes involved in this transformation were recently identified using an RNAi library screen for resistance to pCPTcAMP, a membrane-permeable cyclic AMP analogue that induces differentiation. These molecules, referred to here as posST (positive mediators of STumpy formation), were thereafter validated to regulate the slender to stumpy transition, with many of them apparently comprising part of a signal transduction and effector pathway. However, it is unknown how these proteins act in relation to one another or are ordered within the pathway. To this end, null mutants were created for several posST components in differentiation-competent pleomorphic trypanosomes and, in this genetic background, other members of the predicted pathway expressed to test their ability to restore stumpy formation. Analysis of distinct combinations has been used to build a preliminary pathway structure model for the signalling events underlying trypanosome quorum sensing. In addition, phosphoproteomic analysis of two null mutants has revealed downstream signalling effects of two posST kinases, MEKK1 and YAK. A similar extragenic suppression approach was also applied to explore the interaction between the identified drivers of stumpy formation and the target of rapamycin kinase, TOR4, which has previously been shown to act as a negative regulator of stumpy formation in monomorphs. Dual ablation of TOR4 and posST components revealed insight into the intersection of stumpy-promoting and stumpy-inhibiting pathways. Finally, a chemical-genetic approach was used to investigate the posST pathway using two differentiation-inducing compounds: the previously studied E667, and GKI7, newly identified from a kinase inhibitor set. RNAi lines for different posST components were tested for their ability to undergo development in the presence of these compounds. An RNAi library screen using GKI7 identified putative new mediators of stumpy formation.

Subjects/Keywords: 616.9; brucei; T. brucei; trypanosomes differentiation; signalling

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

APA (6^th Edition):

McDonald, L. M. (2016). Ordering components of the slender to stumpy signalling pathway in Trypanosoma brucei. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/19573

Chicago Manual of Style (16^th Edition):

McDonald, Lindsay Mary. “Ordering components of the slender to stumpy signalling pathway in Trypanosoma brucei.” 2016. Doctoral Dissertation, University of Edinburgh. Accessed April 12, 2021. http://hdl.handle.net/1842/19573.

MLA Handbook (7^th Edition):

McDonald, Lindsay Mary. “Ordering components of the slender to stumpy signalling pathway in Trypanosoma brucei.” 2016. Web. 12 Apr 2021.

Vancouver:

McDonald LM. Ordering components of the slender to stumpy signalling pathway in Trypanosoma brucei. [Internet] [Doctoral dissertation]. University of Edinburgh; 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/1842/19573.

Council of Science Editors:

McDonald LM. Ordering components of the slender to stumpy signalling pathway in Trypanosoma brucei. [Doctoral Dissertation]. University of Edinburgh; 2016. Available from: http://hdl.handle.net/1842/19573

University of Edinburgh

2. Amegatcher, Gloria. Coordination of cell differentiation and mitochondrial development in Trypanosoma brucei.

Degree: PhD, 2019, University of Edinburgh

URL: http://hdl.handle.net/1842/35721

► Trypanosomes are unicellular parasites of humans and livestock, characterised by a single mitochondrion and a highly complex mitochondrial DNA network, the kinetoplast. Trypanosoma brucei causes… (more)

▼ Trypanosomes are unicellular parasites of humans and livestock, characterised by a single mitochondrion and a highly complex mitochondrial DNA network, the kinetoplast. Trypanosoma brucei causes human African trypanosomiasis (HAT, or sleeping sickness) and Nagana in animals, often lethal diseases transmitted by tsetse flies in sub-Saharan Africa. The trypanosome mitochondrial respiratory system involved in energy production comprises of the five classical complexes (I-V); and in addition, a type 2 NADH:ubiquinone oxidoreductase, a glycerol-3-phosphate dehydrogenase and a trypanosome alternative oxidase. Some subunits for respiratory complexes I, III, IV and V are encoded in the kinetoplast DNA. T. brucei encodes genes for complex I; null mutants of complex I (cI) in monomorphic bloodstream form background and RNAi in procyclic cells have not shown any growth defects. Akinetoplastic stumpy cells have shorter life span which could be due to absence of mitochondrially encoded subunits and thus cannot express functional NADH dehydrogenase. Moreover, BF parasites in adipose tissue appear to upregulate pathway for beta-oxidation, which is expected to increase demand for NADH dehydrogenase activity. Little is known about the metabolism and bioenergetics of cI in stumpy forms. Mitochondrial activity changes across the life cycle stages of the parasite. The parasite life stages include slender and stumpy forms (found in the mammalian bloodstream) and procyclic form (found in the tsetse fly). The mammalian bloodstream stage parasite does not express respiratory complexes III and IV and generates most if not all ATP via glycolysis; the insect stage parasite generates most ATP mitochondrially. Thus, coordination of the expression patters for nuclearly and mitochondrially encoded respiratory chain subunits is essential for parasite life cycle progression. In organisms such as yeast, mammals and plants, 'mitochondrial retrograde signalling' pathways, including the 'unfolded protein response (UPRmt), convey information on the functional status of this organelle to the nucleus and modulate expression of nuclear genes accordingly. It is not known if similar signalling pathways exist in trypanosomes. This thesis investigated two questions: 1. Does complex I play an important role in stumpy and/or in cells residing in adipose tissue? 2. Does retrograde signalling pathway exists in T. brucei, lack of mitochondrial genome results in changes in nuclear gene expression? To address the first question, the goal was to generate genetic null mutants for key nuclearly encoded cI subunits (NUBM or NUKM) in pleomorphic (i.e. differentiation competent) Trypanosoma brucei brucei cell line EATRO 1125. Next, the ability of these knockout cell lines to differentiate and to reside in adipose issue would be monitored. Unfortunately, I could not generate a cI null mutant in pleomorphic background as I subsequently determined that the parental cell line used was not fully pleomorphic in mice. Even though the null mutant generated for complex I were not…

Subjects/Keywords: Trypanosoma brucei; T. brucei.; nuclear transcriptome; kinetoplast; stumpy; slender; pleomorphic cell lines; akinetoplastic cell lines

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

APA (6^th Edition):

Amegatcher, G. (2019). Coordination of cell differentiation and mitochondrial development in Trypanosoma brucei. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/35721

Chicago Manual of Style (16^th Edition):

Amegatcher, Gloria. “Coordination of cell differentiation and mitochondrial development in Trypanosoma brucei.” 2019. Doctoral Dissertation, University of Edinburgh. Accessed April 12, 2021. http://hdl.handle.net/1842/35721.

MLA Handbook (7^th Edition):

Amegatcher, Gloria. “Coordination of cell differentiation and mitochondrial development in Trypanosoma brucei.” 2019. Web. 12 Apr 2021.

Vancouver:

Amegatcher G. Coordination of cell differentiation and mitochondrial development in Trypanosoma brucei. [Internet] [Doctoral dissertation]. University of Edinburgh; 2019. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/1842/35721.

Council of Science Editors:

Amegatcher G. Coordination of cell differentiation and mitochondrial development in Trypanosoma brucei. [Doctoral Dissertation]. University of Edinburgh; 2019. Available from: http://hdl.handle.net/1842/35721

University of Georgia

3. Behera, Ranjan Kumar. A hypothesis-generating chemical proteomics approach reveals phosphotyrosine pathways in the African trypanosome.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/28665

► New drugs are needed for human African trypanosomiasis (HAT) caused by subspecies of Trypanosoma brucei as drug resistance and toxic side effects plague current therapies.… (more)

▼ New drugs are needed for human African trypanosomiasis (HAT) caused by subspecies of Trypanosoma brucei as drug resistance and toxic side effects plague current therapies. The phosphotyrosine signaling in trypanosome could be a drug target because it is unique and divergent from the mammalian system. The 4-anilinoquinazoline class of tyrosine kinase inhibitors have been successfully developed as anticancer drugs. From a focused screen of 4-anilinoquinazolines, we discovered GW572016 that kills T. brucei at low micromolar concentrations. We developed a chemical biology approach with GW572016 to gain insight into the phosphotyrosine signaling pathways in the African trypanosome. We also performed a structure-activity relationship study to optimize 4-aninlinoquinazoline scaffold for antitrypanosmal lead drug discovery. Finally, efficacy of select tyrosine kinase inhibitors was tested in a mouse model of acute HAT. GW572016 as a tool inhibits tyrosine phosphorylation of trypanosome proteins. Subsequently, thirty-nine proteins were identified as a part of the GW572016-susceptible phosphotyrosine-signaling pathway. Predicted functions of these proteins include (i) endocytosis (e.g. actin A), (ii) cytoskeleton and cell morphogenesis (e.g. beta-tubulin), and (iii) flagellum biogenesis (e.g. PFR-1/PFR-C). We studied the effects of GW572016 on these three pathways. GW572016 inhibited transferrin endocytosis. Further, the drug causes loss of trypanosome polarity evident from (i) changes in the intracellular localization of beta-tubulin, (ii) redistribution of tyrosylated alpha-tubulin, and (iii) retraction of the flagellum into the cell body. From the 4-anilinoquinazoline scaffold optimization study, we discovered many compounds better (GI50) than GW572016. The in vivo study with tyrosine kinase inhibitors revealed that these compounds could control parasitemia, and they improved mean survival of the treated group. Also, GW572016 could cure the infection in 25% of mice. We propose that 4-anilinoquinazoline is a lead chemical scaffold for antitrypanosome drug discovery.

Subjects/Keywords: Trypanosoma brucei (T. brucei); Human African trypanosomiasis (HAT); Phosphotyrosine signaling; 4-anilinoquinazolines; GW572016 (lapatinib).

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

APA (6^th Edition):

Behera, R. K. (2014). A hypothesis-generating chemical proteomics approach reveals phosphotyrosine pathways in the African trypanosome. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/28665

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Behera, Ranjan Kumar. “A hypothesis-generating chemical proteomics approach reveals phosphotyrosine pathways in the African trypanosome.” 2014. Thesis, University of Georgia. Accessed April 12, 2021. http://hdl.handle.net/10724/28665.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Behera, Ranjan Kumar. “A hypothesis-generating chemical proteomics approach reveals phosphotyrosine pathways in the African trypanosome.” 2014. Web. 12 Apr 2021.

Vancouver:

Behera RK. A hypothesis-generating chemical proteomics approach reveals phosphotyrosine pathways in the African trypanosome. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10724/28665.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Behera RK. A hypothesis-generating chemical proteomics approach reveals phosphotyrosine pathways in the African trypanosome. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/28665

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Georgia

4. Thomas, Sarah Marie. Mode of action of Curaxin-137.

Degree: 2015, University of Georgia

URL: http://hdl.handle.net/10724/31320

► Infection with the protozoan parasite, Trypanosoma brucei, causes a fatal illness known as human African trypanosomiasis (HAT). Drugs necessary to treat HAT have severe limitations… (more)

Subjects/Keywords: Trypanosoma brucei (T. brucei); human African trypanosomiasis (HAT); Drug discovery; Curaxin; CBL0137; DNA replication; kinetoplast

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

APA (6^th Edition):

Thomas, S. M. (2015). Mode of action of Curaxin-137. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/31320

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Thomas, Sarah Marie. “Mode of action of Curaxin-137.” 2015. Thesis, University of Georgia. Accessed April 12, 2021. http://hdl.handle.net/10724/31320.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Thomas, Sarah Marie. “Mode of action of Curaxin-137.” 2015. Web. 12 Apr 2021.

Vancouver:

Thomas SM. Mode of action of Curaxin-137. [Internet] [Thesis]. University of Georgia; 2015. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10724/31320.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Thomas SM. Mode of action of Curaxin-137. [Thesis]. University of Georgia; 2015. Available from: http://hdl.handle.net/10724/31320

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

5. Daiane da Rocha Soares. Modulação de Orc1/Cdc6 de Trypanosoma brucei pela ligação e hidrólise de ATP.

Degree: 2014, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/42/42135/tde-13082014-184135/

►

O Complexo de pré-replicação em T.brucei é composto por Orc1/Cdc6 e as helicases MCMs. Em um trabalho anterior mostramos que TbOrc1/Cdc6 pode ligar e hidrolisar… (more)

▼

O Complexo de pré-replicação em T.brucei é composto por Orc1/Cdc6 e as helicases MCMs. Em um trabalho anterior mostramos que TbOrc1/Cdc6 pode ligar e hidrolisar ATP in vitro. Neste sentido, o objetivo deste trabalho é avaliar a importância da hidrólise e ligação de ATP para a formação e estabilidade do complexo pré-replicação de T.brucei. Para tanto, foram geradas proteínas recombinantes Orc1/Cdc6 de T. brucei mutadas nas regiões Walker A (TbOrc1/Cdc6K79T) ou sensor 2 (TbOrc1/Cdc6R251,252E) incapazes de ligar ou hidrolisar ATP, respectivamente. Finalmente, as células expressando TbOrc1/Cdc6K79T ou TbOrc1/Cdc6R251,252E foram avaliadas quanto a (i ) estabilidade da interação Orc1/Cdc6 -DNA, (ii) capacidade de estabilizar MCM no DNA, (iii) capacidade de replicar seu DNA. A mutação na região sensor 2 de T.brucei (TbOrc1/Cdc6R251,252E) reduziu drasticamente a atividade de ATPase em comparação com a proteína selvagem . TbOrc1/Cdc6 mutado no sitio de ligação ao ATP perdeu a capacidade de interagir com o ATP (TbOrc1/Cdc6K79T). A super expressão desses genes inibiu de forma significativa a proliferação celular, causou ineficiência no carregamento de MCM para o DNA e ocasionou falhas na progressão do ciclo celular, atrasando a fase S.

The pre-replication complex in T.brucei is composed of at Orc1/Cdc6 and MCMs helicases. In a previous paper we showed that TbOrc1/Cdc6 can bind and hydrolyze ATP in vitro. Based on that, the objective of this study is to evaluate the importance of ATP binding and hydrolysis to the formation and stability of the pre - replication complex in T.brucei. For this purpose, T. brucei Orc1/Cdc6 recombinant proteins were generated mutated at regions on Walker A (TbOrc1/Cdc6K79T) and sensor 2 (TbOrc1/Cdc6R251 , 252E) in order to unable the ATP binding and hydrolyzation respectively . Finally , cells expressing TbOrc1/Cdc6K79T or TbOrc1/Cdc6R251 , 252E were evaluated for (i) stability of Orc1/Cdc6 - DNA interaction , (ii) ability to stabilize MCM in DNA , (iii) ability to replicate its DNA . The mutation in the sensor 2 region of T.brucei (TbOrc1/Cdc6R251 , 252E) drastically reduced the ATPase activity compared to the wild-type protein. TbOrc1/Cdc6 mutated in the ATP binding site has lost the ability to interact with ATP (TbOrc1/Cdc6K79T). The overexpression of these genes significantly inhibited cell proliferation causing inefficient loading of MCM DNA and led to failure in cell cycle progression by delaying the phase S.

Advisors/Committee Members: Maria Carolina Quartim Barbosa Elias Sabbaga, Bettina Malnic, Gerhard Wunderlich.

Subjects/Keywords: T. brucei; ATP; ATPase; DNA; Origem de replicação; Replicação do DNA; T. brucei; ATP; ATPase; DNA; DNA replication; Origin of replication

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

APA (6^th Edition):

Soares, D. d. R. (2014). Modulação de Orc1/Cdc6 de Trypanosoma brucei pela ligação e hidrólise de ATP. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/42/42135/tde-13082014-184135/

Chicago Manual of Style (16^th Edition):

Soares, Daiane da Rocha. “Modulação de Orc1/Cdc6 de Trypanosoma brucei pela ligação e hidrólise de ATP.” 2014. Masters Thesis, University of São Paulo. Accessed April 12, 2021. http://www.teses.usp.br/teses/disponiveis/42/42135/tde-13082014-184135/.

MLA Handbook (7^th Edition):

Soares, Daiane da Rocha. “Modulação de Orc1/Cdc6 de Trypanosoma brucei pela ligação e hidrólise de ATP.” 2014. Web. 12 Apr 2021.

Vancouver:

Soares DdR. Modulação de Orc1/Cdc6 de Trypanosoma brucei pela ligação e hidrólise de ATP. [Internet] [Masters thesis]. University of São Paulo; 2014. [cited 2021 Apr 12]. Available from: http://www.teses.usp.br/teses/disponiveis/42/42135/tde-13082014-184135/.

Council of Science Editors:

Soares DdR. Modulação de Orc1/Cdc6 de Trypanosoma brucei pela ligação e hidrólise de ATP. [Masters Thesis]. University of São Paulo; 2014. Available from: http://www.teses.usp.br/teses/disponiveis/42/42135/tde-13082014-184135/

University of Bath

6. Game, Stephen. Sugar transport in Trypanosoma brucei.

Degree: PhD, 1988, University of Bath

URL: https://researchportal.bath.ac.uk/en/studentthesis/sugar-transport-in-trypanosoma-brucei(72f33ae1-9dd2-4f3d-8d80-d1a4609217d0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383248

Subjects/Keywords: 572; Biochemistry of T. brucei

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

APA (6^th Edition):

Game, S. (1988). Sugar transport in Trypanosoma brucei. (Doctoral Dissertation). University of Bath. Retrieved from https://researchportal.bath.ac.uk/en/studentthesis/sugar-transport-in-trypanosoma-brucei(72f33ae1-9dd2-4f3d-8d80-d1a4609217d0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383248

Chicago Manual of Style (16^th Edition):

Game, Stephen. “Sugar transport in Trypanosoma brucei.” 1988. Doctoral Dissertation, University of Bath. Accessed April 12, 2021. https://researchportal.bath.ac.uk/en/studentthesis/sugar-transport-in-trypanosoma-brucei(72f33ae1-9dd2-4f3d-8d80-d1a4609217d0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383248.

MLA Handbook (7^th Edition):

Game, Stephen. “Sugar transport in Trypanosoma brucei.” 1988. Web. 12 Apr 2021.

Vancouver:

Game S. Sugar transport in Trypanosoma brucei. [Internet] [Doctoral dissertation]. University of Bath; 1988. [cited 2021 Apr 12]. Available from: https://researchportal.bath.ac.uk/en/studentthesis/sugar-transport-in-trypanosoma-brucei(72f33ae1-9dd2-4f3d-8d80-d1a4609217d0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383248.

Council of Science Editors:

Game S. Sugar transport in Trypanosoma brucei. [Doctoral Dissertation]. University of Bath; 1988. Available from: https://researchportal.bath.ac.uk/en/studentthesis/sugar-transport-in-trypanosoma-brucei(72f33ae1-9dd2-4f3d-8d80-d1a4609217d0).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383248

SUNY College at Brockport

7. Frainier, Alyssa S. Characterization of TbLpn in Trypanosoma brucei.

Degree: MS, Biology, 2012, SUNY College at Brockport

URL: https://digitalcommons.brockport.edu/bio_theses/9

► Trypanosoma brucei, is a flagellated, unicellular, parasitic protozoan transmitted by the tsetse fly. It is the source of African sleeping sickness in humans. African… (more)

▼ Trypanosoma brucei, is a flagellated, unicellular, parasitic protozoan transmitted by the tsetse fly. It is the source of African sleeping sickness in humans. African sleeping sickness has two different stages, the bloodstream and central nervous system stages, each characterized by different symptoms. Problems with treatment result from severe side effects of the drugs used to treat African sleeping sickness. No vaccine is available due to high antigenic variation. T. brucei exists as two forms. The procyclic fly form relies on oxidative phosphorylation, expresses procyclin as its surface protein, and is morphologically long and slender. In contrast, the mammalian bloodstream form expresses the surface protein VSG, and is characterized as short and stumpy. In T. brucei, gene regulation is controlled primarily at the post-transcriptional level, thus RNA binding proteins play a role in gene regulation. Some RNA binding proteins serve as substrates for enzymes known as protein arginine methyltransferases (PRMTs). These enzymes specifically methylate arginine residues on proteins. A yeast two hybrid approach was used to identify proteins interacting with TbPRMT1 in T. brucei. Among the proteins shown to interact with TbPRMT1, one is a homolog of yeast and mammalian lipin proteins. This protein, which is termed Tblpn, has 2 conserved domains characteristic of lipin proteins. In addition, 2 aspartic acid residues were conserved in T. brucei. Lipin is involved in adipocyte development in mice. A mutation of lipin causes decreased adipocyte development associated with fatty liver dystrophy. Overexpression of the protein results in obesity in mice. Lipin also plays an important role in fatty acid synthesis and signaling in yeast, but possibly relates to the development of important phospholipids in T. brucei, specifically phosphatidylethanolamine and phosphatidylcholine. The objectives of my project were to determine where TbLpn is localized in the cell, to determine whether TbLpn interacts with TbPRMT1 in vivo, and finally to determine if TbLpn is methylated in vivo.

Subjects/Keywords: T. brucei; African Sleeping Sickness; tsetse fly; treatment; genetics; Parasitology

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

APA (6^th Edition):

Frainier, A. S. (2012). Characterization of TbLpn in Trypanosoma brucei. (Thesis). SUNY College at Brockport. Retrieved from https://digitalcommons.brockport.edu/bio_theses/9

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Frainier, Alyssa S. “Characterization of TbLpn in Trypanosoma brucei.” 2012. Thesis, SUNY College at Brockport. Accessed April 12, 2021. https://digitalcommons.brockport.edu/bio_theses/9.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Frainier, Alyssa S. “Characterization of TbLpn in Trypanosoma brucei.” 2012. Web. 12 Apr 2021.

Vancouver:

Frainier AS. Characterization of TbLpn in Trypanosoma brucei. [Internet] [Thesis]. SUNY College at Brockport; 2012. [cited 2021 Apr 12]. Available from: https://digitalcommons.brockport.edu/bio_theses/9.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Frainier AS. Characterization of TbLpn in Trypanosoma brucei. [Thesis]. SUNY College at Brockport; 2012. Available from: https://digitalcommons.brockport.edu/bio_theses/9

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Edinburgh

8. Carloni, Roberta. Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei.

Degree: PhD, 2014, University of Edinburgh

URL: http://hdl.handle.net/1842/18015

► In order to evaluate the suitability of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) as a potential drug target for an anti-parasite therapy, we… (more)

Subjects/Keywords: 572.8; DNA repair; topoisomerase; TDP1; tyrosyl-DNA phosphodiesterase 1; T. brucei

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

APA (6^th Edition):

Carloni, R. (2014). Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/18015

Chicago Manual of Style (16^th Edition):

Carloni, Roberta. “Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei.” 2014. Doctoral Dissertation, University of Edinburgh. Accessed April 12, 2021. http://hdl.handle.net/1842/18015.

MLA Handbook (7^th Edition):

Carloni, Roberta. “Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei.” 2014. Web. 12 Apr 2021.

Vancouver:

Carloni R. Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei. [Internet] [Doctoral dissertation]. University of Edinburgh; 2014. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/1842/18015.

Council of Science Editors:

Carloni R. Functional analysis of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) in Trypanosoma brucei brucei. [Doctoral Dissertation]. University of Edinburgh; 2014. Available from: http://hdl.handle.net/1842/18015

University of Georgia

9. Patham, Bhargavi. Protein translocation across endoplasmic reticulum of a trypanosome.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/22750

► Despite being recognized as an important organelle in the secretory pathway, not many aspects of endoplasmic reticulum (ER) protein import are understood in Trypanosoma brucei,… (more)

▼ Despite being recognized as an important organelle in the secretory pathway, not many aspects of endoplasmic reticulum (ER) protein import are understood in Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Movement of proteins into the ER requires a signal sequence and a Sec61p translocation pore. We have developed a cell-free system using T. brucei microsomes (TbRM) and variant surface glycoprotein (VSG) as our model substrate. TbRM could import full-length proteins post-translationally in a parasitecytosol dependent fashion. Purified Hsp70 (Ssa1p) could replace parasite cytosol in assisting protein translocation into TbRM, suggesting a role of molecular chaperones in protein translocation into ER of trypanosomes. Protein import into TbRM was signal peptide dependent. Further, model proteins from Escherichia coli, Saccharomyces cerevisiae and Bos taurus were not imported into TbRM. Conversely, many trypanosomatid proteins were not imported into canine microsomes. Since signal peptides are selectively recognized by specific translocation machineries, we hypothesize that signal peptides have ‘co-evolved” with their translocons.We used the in vitro system to identify protein translocation blockers (PTBs), compounds that inhibit parasite protein import into TbRM. PTBs (MAL3-101, equisetin and CJ-21, 058) were trypanocidal, with IC50 (the concentration at which fifty percent of parasites are killed) of; 125 nM (MAL3-101), 3.3 µM (equisetin) and 7 µM (CJ-21, 058). PTBs did not affect viability of a model mammalian cell. Therefore, we have i) identified ER protein translocation machinery, as a drug target in T. brucei, and ii) discovered trypanocidal compounds that may act on import of proteins into the parasite ER. Signal sequences have three conserved regions; an amino-terminal (n-region), a hydrophobic (h-region), and a carboxy-terminal (c-region). Although the hydrophobic core is important for efficient import/export of proteins, functional characteristics of h-regions are poorly understood. A bioinformatics analysis led to the discovery of highly conserved peptide motifs in h-region of signal sequences in eukaryotes (h. sapiens, S. cerevisiae, T. brucei), and prokaryotes (E. coli, B. subtilis). Peptide motifs in h-regions may significantly contribute to signal sequence activity. Finally, amino acids in h-region of signal sequences are not randomly selected. On the contrary, selection and distribution of amino acids in h-regions is highly specific to, and varies across species.

Subjects/Keywords: Endoplasmic Reticulum; Human African Trypanosomiasis; Protein translocation blockers; Trypanosoma brucei; T. brucei microsomes; Variant surface glycoprotein

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

APA (6^th Edition):

Patham, B. (2014). Protein translocation across endoplasmic reticulum of a trypanosome. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/22750

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Patham, Bhargavi. “Protein translocation across endoplasmic reticulum of a trypanosome.” 2014. Thesis, University of Georgia. Accessed April 12, 2021. http://hdl.handle.net/10724/22750.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Patham, Bhargavi. “Protein translocation across endoplasmic reticulum of a trypanosome.” 2014. Web. 12 Apr 2021.

Vancouver:

Patham B. Protein translocation across endoplasmic reticulum of a trypanosome. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10724/22750.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Patham B. Protein translocation across endoplasmic reticulum of a trypanosome. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/22750

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Edinburgh

10. Hide, Geoffrey. Variation in repetitive DNA in African Trypanosomes.

Degree: PhD, 1988, University of Edinburgh

URL: http://hdl.handle.net/1842/12083

Subjects/Keywords: 572.8; Genetic variation in T. brucei

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

APA (6^th Edition):

Hide, G. (1988). Variation in repetitive DNA in African Trypanosomes. (Doctoral Dissertation). University of Edinburgh. Retrieved from http://hdl.handle.net/1842/12083

Chicago Manual of Style (16^th Edition):

Hide, Geoffrey. “Variation in repetitive DNA in African Trypanosomes.” 1988. Doctoral Dissertation, University of Edinburgh. Accessed April 12, 2021. http://hdl.handle.net/1842/12083.

MLA Handbook (7^th Edition):

Hide, Geoffrey. “Variation in repetitive DNA in African Trypanosomes.” 1988. Web. 12 Apr 2021.

Vancouver:

Hide G. Variation in repetitive DNA in African Trypanosomes. [Internet] [Doctoral dissertation]. University of Edinburgh; 1988. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/1842/12083.

Council of Science Editors:

Hide G. Variation in repetitive DNA in African Trypanosomes. [Doctoral Dissertation]. University of Edinburgh; 1988. Available from: http://hdl.handle.net/1842/12083

11. Τsatsaroni, Alexandra. Σπειροκαρβοκυκλικά και αρυλοϋποκατεστημένα 2,6-δικετοπιπεραζινο-1-ακετοϋδροξαμικά και σπειροκαρβοκυκλικά Ν-[(2,6-δικετοπιπεραζιν-1-υλ)ακετυλο] γλυκινοϋδροξαμικά οξέα: σχεδιασμός, σύνθεση και αξιολόγηση της αντιτυπανοσωμιακής in vitro δράσης.

Degree: 2016, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/39815

► The present PhD thesis refers to the design, synthesis and evaluation of the in vitro anti-trypanosomal activity of new spirocarbocyclic (adamantano, cyclooctano and cycloheptano derivatives),… (more)

▼ The present PhD thesis refers to the design, synthesis and evaluation of the in vitro anti-trypanosomal activity of new spirocarbocyclic (adamantano, cyclooctano and cycloheptano derivatives), 2,6-diketopiperazino-1-acetohydroxamic acids (compounds 1-6), 3-alkyl-3-aryl-2,6-diketopiparazino-1- acetohydroxamic acids (compounds 7-18) and spirocarbocyclic N-[(2,6-diketopiperazin-1-yl)glycine hydroxamic acids (compounds 19-29). The rationale behind the design of compounds 1-18, was based on our previous findings according to which the introduction of the acetohydroxamic moiety (CH2CONHOH) on the imidic nitrogen atom of lipophilic spirocarbocyclic 2,6-diketopiperazine scaffolds, leads to very potent trypanocidals (IC50 6.8-1870 nΜ, compounds VIIIa-e, IX, Xa-d, XΙa and XIb, Table 1). Analogues 1-4 were synthesized in order to investigate whether the structural features of the substituent on the methylenic carbon, near the basic nitrogen atom of the 2,6-diketopiperazino ring, have an effect on the antitrypanosomal activity. Moreover, the synthesis of the N-methylhydroxamic acids (2o hydroxamic acids 5 and 6) aimed at probing the influence of the methyl substitution on the conformation of the carbohydroxamic group and hence the antitrypanosomal activity of the spirocarbocyclic 2,6-diketopiperazino-1-acetohydroxamic acids. The structural modification, which involves the replacement of the spiro-linked carbocyclic ring by benzene (substituted and unsubstituted) and an alkyl substituent (CH3, (CH2)2CH3, (CH2)3CH3), led to the design of compounds 7-18. In a previous publication we demonstrated that the presence of the acetohydroxamic group in compounds VIIIa-e, IX, Xa-d, XΙa and XIb constitutes a prerequisite for trypanocidal activity, which was linked to the ability of these molecules to inhibit a metalloenzyme, by trapping the metal ion on its active centre. Thus, in order to augment the formation of a carbohydroxamic-enzymic metal ion complex, the acetohydroxamic moiety (CH2CONHOH) was replaced by an N-acetoglycine hydroxamic residue (CH2CON(R)CH2CONHOH). The introduction of this functionality was hoped to lead to an enhanced complex stabilisation, due to additional interactions between the acetamido portion (CH2CONR) and the biological target(s) in the active centre’s nearby sites. Based on this assumption compounds 19-29 were designed and synthesised.The carboxylic acids 43-45 (Scheme 4), 59, 60 (Scheme 5), 83-86 (Scheme 8), 107-110 (Scheme 9), 124 and 125 (Scheme 10), are precursors of the target molecules 1, 3-6, 7, 8, 10-13, 15-18 and were synthesised by following the appropriate methodologies we have previously developed. Thus, the coupling of the aforementioned carboxylic acids with O-benzylhydroxylamine or O-benzyl-N-methylhydroxylamine, in the presence of 1,1’-carbonyldiimidazole (CDI), leads to to the O-benzylcarbohydroxamic derivatives 46, 48, 49, 61, 62, 87, 88, 90, 91, 111, 112, 114, 115, 126 and 127. Hydrogenolysis of their benzyl group gives the acetohydroxamic acids 1, 3-6, 7, 8, 10-13, 15-18. The synthesis of…

Subjects/Keywords: Τρυπανοσωμίαση; Αφρικανικό τρυπανόσωμα (Τ. brucei); Υδροξαμικά οξέα; Ε/Ζ διαμορφομερή; Κύτταρα θηλαστικών (L6-κύτταρα αρουραίου); Trypanosomiasis; African trypanosoma (T. brucei); Hydroxamic acids; E/Z conformations; Mammalian rat L6-cells

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

APA (6^th Edition):

Τsatsaroni, A. (2016). Σπειροκαρβοκυκλικά και αρυλοϋποκατεστημένα 2,6-δικετοπιπεραζινο-1-ακετοϋδροξαμικά και σπειροκαρβοκυκλικά Ν-[(2,6-δικετοπιπεραζιν-1-υλ)ακετυλο] γλυκινοϋδροξαμικά οξέα: σχεδιασμός, σύνθεση και αξιολόγηση της αντιτυπανοσωμιακής in vitro δράσης. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/39815

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Τsatsaroni, Alexandra. “Σπειροκαρβοκυκλικά και αρυλοϋποκατεστημένα 2,6-δικετοπιπεραζινο-1-ακετοϋδροξαμικά και σπειροκαρβοκυκλικά Ν-[(2,6-δικετοπιπεραζιν-1-υλ)ακετυλο] γλυκινοϋδροξαμικά οξέα: σχεδιασμός, σύνθεση και αξιολόγηση της αντιτυπανοσωμιακής in vitro δράσης.” 2016. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed April 12, 2021. http://hdl.handle.net/10442/hedi/39815.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Τsatsaroni, Alexandra. “Σπειροκαρβοκυκλικά και αρυλοϋποκατεστημένα 2,6-δικετοπιπεραζινο-1-ακετοϋδροξαμικά και σπειροκαρβοκυκλικά Ν-[(2,6-δικετοπιπεραζιν-1-υλ)ακετυλο] γλυκινοϋδροξαμικά οξέα: σχεδιασμός, σύνθεση και αξιολόγηση της αντιτυπανοσωμιακής in vitro δράσης.” 2016. Web. 12 Apr 2021.

Vancouver:

Τsatsaroni A. Σπειροκαρβοκυκλικά και αρυλοϋποκατεστημένα 2,6-δικετοπιπεραζινο-1-ακετοϋδροξαμικά και σπειροκαρβοκυκλικά Ν-[(2,6-δικετοπιπεραζιν-1-υλ)ακετυλο] γλυκινοϋδροξαμικά οξέα: σχεδιασμός, σύνθεση και αξιολόγηση της αντιτυπανοσωμιακής in vitro δράσης. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2016. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10442/hedi/39815.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Τsatsaroni A. Σπειροκαρβοκυκλικά και αρυλοϋποκατεστημένα 2,6-δικετοπιπεραζινο-1-ακετοϋδροξαμικά και σπειροκαρβοκυκλικά Ν-[(2,6-δικετοπιπεραζιν-1-υλ)ακετυλο] γλυκινοϋδροξαμικά οξέα: σχεδιασμός, σύνθεση και αξιολόγηση της αντιτυπανοσωμιακής in vitro δράσης. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2016. Available from: http://hdl.handle.net/10442/hedi/39815

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Rockefeller University

12. Dreesen, Oliver. Telomere Structure and Shortening in Telomerase-Deficient Trypanosoma brucei: Implications for Anitgenic Variation.

Degree: 2006, Rockefeller University

URL: https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/50

► A variety of parasites persist in their host through sequential expression of variant surface antigens. Intriguingly, the genes encoding these antigens are frequently found… (more)

▼ A variety of parasites persist in their host through sequential expression of variant surface antigens. Intriguingly, the genes encoding these antigens are frequently found adjacent to the telomeres. Telomeres are nucleoprotein complexes consisting of tandem DNA repeats and proteins that bind to them. Their function is to protect chromosome ends from the DNA repair machinery that would otherwise recognize them as double-stranded breaks. With the help of the ribonucleoprotein telomerase they compensate for the gradual sequence loss that would otherwise arise from the inability of conventional DNA polymerases to replicate chromosome ends. In Trypanosoma brucei, the causative agent of African trypanosomiasis, the surface coat consists of a dense layer of Variant Surface Glycoproteins (VSG). The actively transcribed VSG is found in one of ~20 telomeric Expression Sites (ES). Antigenic variation can occur by transcriptional switching, reciprocal translocations, or duplicative gene conversion events between ES. In recent African isolates, duplicative gene conversion occurs at a high frequency and predominates, but the switching frequency decreases dramatically upon laboratory-adaptation. Very little is known about the regulation of antigenic variation. To address whether telomeres are involved in antigenic switching we created telomerasedeficient T. brucei. Telomerase-deficient parasites exhibited progressive telomere shortening at a rate of 3â€“6 bp/PD, which correlates with the end replication problem and G-overhang length. Upon reaching a critical length, short silent ES telomeres stabilized. Telomere decline was accompanied by loss of minichromosomes and rearrangements at intermediate chromosomes. Essential megabase chromosomes remained stable. After extensive telomere attrition, the active ES telomere stabilized, but the transcribed VSG was gradually lost from the population and replaced by a new VSG through duplicative gene conversion. We present a model in which subtelomeric break-induced replication-mediated repair at a short ES telomere leads to duplicative gene conversion and expression of a new VSG. By restoring telomerase, we studied telomere elongation dynamics. At the active ES, the rate of telomere elongation is inversely proportional to the initial telomere length. At silent ES, the rate of elongation remains constant. We propose a model where transcription-dependent chromatin remodeling permits telomere elongation by telomerase. We show that telomere growth at a rate of 6â€“8 bp/PD appears to be a unique feature of T. brucei. Lastly we demonstrate that fast-switching African T. brucei isolates have dramatically shorter telomeres than laboratory strains. We present a speculative model in which telomere growth and breakage affect the rate of antigenic switching.

Subjects/Keywords: trypanosoma brucei; African T. brucei; African sleeping sickness; telomere shortening; Life Sciences

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

APA (6^th Edition):

Dreesen, O. (2006). Telomere Structure and Shortening in Telomerase-Deficient Trypanosoma brucei: Implications for Anitgenic Variation. (Masters Thesis). Rockefeller University. Retrieved from https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/50

Chicago Manual of Style (16^th Edition):

Dreesen, Oliver. “Telomere Structure and Shortening in Telomerase-Deficient Trypanosoma brucei: Implications for Anitgenic Variation.” 2006. Masters Thesis, Rockefeller University. Accessed April 12, 2021. https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/50.

MLA Handbook (7^th Edition):

Dreesen, Oliver. “Telomere Structure and Shortening in Telomerase-Deficient Trypanosoma brucei: Implications for Anitgenic Variation.” 2006. Web. 12 Apr 2021.

Vancouver:

Dreesen O. Telomere Structure and Shortening in Telomerase-Deficient Trypanosoma brucei: Implications for Anitgenic Variation. [Internet] [Masters thesis]. Rockefeller University; 2006. [cited 2021 Apr 12]. Available from: https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/50.

Council of Science Editors:

Dreesen O. Telomere Structure and Shortening in Telomerase-Deficient Trypanosoma brucei: Implications for Anitgenic Variation. [Masters Thesis]. Rockefeller University; 2006. Available from: https://digitalcommons.rockefeller.edu/student_theses_and_dissertations/50

13. Rocha, Débora Assumpção. Síntese de inibidores de cruzaína e rodesaína.

Degree: 2018, Brazil

URL: http://hdl.handle.net/10183/201155

►

As doenças de Chagas e do Sono Africana são doenças negligenciadas, tendo como agente etiológico Trypanosoma cruzi e Trypanosoma brucei, respectivamente. Uma classe de alvos… (more)

▼

As doenças de Chagas e do Sono Africana são doenças negligenciadas, tendo como agente etiológico Trypanosoma cruzi e Trypanosoma brucei, respectivamente. Uma classe de alvos terapêuticos validados para o tratamento destas doenças são as proteases, como cruzaína, principal cisteíno-protease (CP) do T. cruzi e rodesaína, principal CP do T. brucei. Numa triagem experimental de compostos de bases comerciais foi identificado o composto intitulado PH100 como potencial inibidor reversível destas enzimas. Utilizando High-Throughput Virtual Screening, docking XP e modificações clássicas de química medicinal, priorizamos derivados de PH100 para síntese. Neste trabalho foi feita a síntese de 10 derivados quinazolínicos, 2 pirimidínicos e 2 purínicos. Para a síntese dos quinazolínicos, o ácido antranílico 11 foi reagido com uréia, fornecendo a dioxaquinazolina 12, que sofreu uma dicloração nas posições 2 e 4 do anel utilizando POCl3 e DMA, resultando na 2,4-dicloroquinazolina 13. Em seguida, foi feita uma substituição nucleofílica aromática (SNA) utilizando benzilamina, seletivamente na posição 4, formando o intermediário 14. Por último, uma substituição com diferentes aminas na posição 2 do anel obtendo os 10 derivados quinazolínicos 2,4-dissubstituídos. Para obter os derivados PH100-103 e PH106-107 foi feita uma SNA com a amina apropriada em EtOH, enquanto para PH104-105 e PH108-109 o acoplamento foi feito através do Cross-coupling de Buchwald-Hartwig. Os compostos pirimidínicos foram obtidos a partir da 2,4-dicloropirimidina 16, nas mesmas condições anteriores. Para os purínicos, partimos da 2,6-dicloro-9H-purina 18 sendo metilada utilizando ICH3 e K2CO3. A 2,6-dicloro-9-metil-9H-purina 19 resultante sofreu uma SNA com benzilamina, formando o intermediário 20. Por último, fizemos uma reação de Cross-coupling obtendo PH111 e PH113. Os compostos foram testados quanto a sua atividade inibitória frente cruzaína e rodesaína: PH100 e PH107 apresentaram os melhores valores de IC50 para cruzaína e PH105 e PH107 para rodesaína. No ensaio contra T.cruzi, PH106 e PH107 obtiveram os melhores resultados, este último com um IC50 de 0,1 μM e com um bom índice de seletividade.

Chagas disease and Human African trypanosomiasis (HAT), whose etiological agent are Trypanosoma cruzi and Trypanosoma brucei, respectively, are neglected diseases. One of the validated drug target class for the treatment of these diseases are proteases, such as cruzain, the main T. cruzi cysteine protease (CP), and rhodesain, the main CP of T. brucei. After a screening with commercially available compounds from database, we have identified the compound named PH100 as a potential reversible inhibitor of these enzymes. Next, we have prioritized its derivatives using High–Throughput Virtual Screening, docking XP or classical medicinal chemistry modifications. In this work, we have synthesized 10 quinazolinic, 2 pyrimidinic and 2 purinic derivatives. In the synthesis of the quinazolinic derivatives, anthranilic acid 11 was reacted with urea, providing 2,4…

Advisors/Committee Members: Andrade, Saulo Fernandes de, Ferreira, Rafaela Salgado.

Subjects/Keywords: Doença de Chagas; Tripanossomiase africana; Trypanosoma cruzi; Chagas disease; Human african trypanosomiasis; T. brucei; Cruzain; Rhodesain; Reversible inhibitors; Buchwald-Hartwig reaction

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

APA (6^th Edition):

Rocha, D. A. (2018). Síntese de inibidores de cruzaína e rodesaína. (Masters Thesis). Brazil. Retrieved from http://hdl.handle.net/10183/201155

Chicago Manual of Style (16^th Edition):

Rocha, Débora Assumpção. “Síntese de inibidores de cruzaína e rodesaína.” 2018. Masters Thesis, Brazil. Accessed April 12, 2021. http://hdl.handle.net/10183/201155.

MLA Handbook (7^th Edition):

Rocha, Débora Assumpção. “Síntese de inibidores de cruzaína e rodesaína.” 2018. Web. 12 Apr 2021.

Vancouver:

Rocha DA. Síntese de inibidores de cruzaína e rodesaína. [Internet] [Masters thesis]. Brazil; 2018. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/10183/201155.

Council of Science Editors:

Rocha DA. Síntese de inibidores de cruzaína e rodesaína. [Masters Thesis]. Brazil; 2018. Available from: http://hdl.handle.net/10183/201155

New Jersey Institute of Technology

14. Bucci, Brett. RNA genome annotation with a focus on T. brucei.

Degree: MSin Computational Biology - (M.S.), Computer Science, 2008, New Jersey Institute of Technology

URL: https://digitalcommons.njit.edu/theses/323

► The goal of this project is to identify untranslated regions (UTRs) and UTR-indicating patterns in the genome of T. brucei. T. brucei is an… (more)

Subjects/Keywords: RNA genome; T. brucei; African sleeping sickness; Biostatistics; Computer Sciences

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

APA (6^th Edition):

Bucci, B. (2008). RNA genome annotation with a focus on T. brucei. (Thesis). New Jersey Institute of Technology. Retrieved from https://digitalcommons.njit.edu/theses/323

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bucci, Brett. “RNA genome annotation with a focus on T. brucei.” 2008. Thesis, New Jersey Institute of Technology. Accessed April 12, 2021. https://digitalcommons.njit.edu/theses/323.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bucci, Brett. “RNA genome annotation with a focus on T. brucei.” 2008. Web. 12 Apr 2021.

Vancouver:

Bucci B. RNA genome annotation with a focus on T. brucei. [Internet] [Thesis]. New Jersey Institute of Technology; 2008. [cited 2021 Apr 12]. Available from: https://digitalcommons.njit.edu/theses/323.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bucci B. RNA genome annotation with a focus on T. brucei. [Thesis]. New Jersey Institute of Technology; 2008. Available from: https://digitalcommons.njit.edu/theses/323

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

15. Rivera, Sylvia L. Trypanosoma Brucei Mitochondrial DNA POLIB Cell Cycle Localization and Effect on POLIC when POLIB is Depleted.

Degree: University of Massachusetts

URL: https://scholarworks.umass.edu/masters_theses_2/442

► Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (HAT), also known as African sleeping sickness. T. brucei is unique in several ways… (more)

▼ Trypanosoma brucei is the causative agent of Human African Trypanosomiasis (HAT), also known as African sleeping sickness. T. brucei is unique in several ways that distinguish this organism from other eukaryotes. One of the unique features of T. brucei is the organism’s mitochondrial DNA, which is organized in a complex structure called kinetoplast DNA (kDNA). Since kDNA is unique to the kinetoplastids, kDNA may serve as a good drug target against T. brucei. Previews studies have shown that kDNA has 4 different family A mitochondrial DNA polymerases. Three of these mitochondrial DNA polymerases (POLIB, POLIC, and POLID) are essential components of kDNA synthesis and replication. POLID and POLIC dynamically localize throughout the cell cycle. POLID is found dispersed in the matrix before the kDNA has undergone replication and is re-localized at the antipodal sites when the kDNA is dividing. POLIC is found in the kinetoflagellar zone (KFZ) at low concentrations when the kDNA is not replicating and relocalizes to the antipodal sites when dividing. Based on the dynamic localization of these two DNA polymerases, we hypothesize that POLIB undergoes dynamic localization at some point during the cell cycle stage. Here, a POLIB/PTP single expressor cell line was analyzed by immunofluorescence microscopy in an unsynchronized population. We characterized the localization pattern of POLIB-PTP at different cell cycle stages and found different localization patterns throughout cell cycle. Cells at 1N1K (the majority of cell in an unsynchronized population) have single foci, but at 1N1K_divtwo different patterns are mainly observed, diffuse and segregated. When the kDNAs are separated POLIB-PTP is again seen as a distinct foci in each kDNA. By doing TdT labeling and a quantitative analysis, we found that at early stages of minicircles replication POLIB-PTP start relocalizing to the kDNA disk with a diffuse pattern being the main. By the time the minicircles are being reattached in the disk (late TdT), POLIB is seen in the disk as a bilobe shape. Advisors/Committee Members: Michele M Klingbeil, Steve Sandler, Yasu Morita.

Subjects/Keywords: T. brucei; POLIB; POLIC; polymerases; mitochondrial DNA; kDNA; Life Sciences; Microbiology; Pathogenic Microbiology

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APA (6^th Edition):

Rivera, S. L. (n.d.). Trypanosoma Brucei Mitochondrial DNA POLIB Cell Cycle Localization and Effect on POLIC when POLIB is Depleted. (Thesis). University of Massachusetts. Retrieved from https://scholarworks.umass.edu/masters_theses_2/442

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rivera, Sylvia L. “Trypanosoma Brucei Mitochondrial DNA POLIB Cell Cycle Localization and Effect on POLIC when POLIB is Depleted.” Thesis, University of Massachusetts. Accessed April 12, 2021. https://scholarworks.umass.edu/masters_theses_2/442.

Note: this citation may be lacking information needed for this citation format:
No year of publication.
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rivera, Sylvia L. “Trypanosoma Brucei Mitochondrial DNA POLIB Cell Cycle Localization and Effect on POLIC when POLIB is Depleted.” Web. 12 Apr 2021.

Note: this citation may be lacking information needed for this citation format:
No year of publication.

Vancouver:

Rivera SL. Trypanosoma Brucei Mitochondrial DNA POLIB Cell Cycle Localization and Effect on POLIC when POLIB is Depleted. [Internet] [Thesis]. University of Massachusetts; [cited 2021 Apr 12]. Available from: https://scholarworks.umass.edu/masters_theses_2/442.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

Council of Science Editors:

Rivera SL. Trypanosoma Brucei Mitochondrial DNA POLIB Cell Cycle Localization and Effect on POLIC when POLIB is Depleted. [Thesis]. University of Massachusetts; Available from: https://scholarworks.umass.edu/masters_theses_2/442

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
No year of publication.

16. Katz, Rodolfo. Análise computacional de candidatos a homólogos a fatores de iniciação da tradução em tripanossomatídeos.

Degree: 2006, Universidade Federal de Pernambuco

URL: https://repositorio.ufpe.br/handle/123456789/6513

► A síntese protéica é um processo básico e essencial para a sobrevivência dos seres vivos. Um dos pontos chave deste processo é a etapa de… (more)

▼ A síntese protéica é um processo básico e essencial para a sobrevivência dos seres vivos. Um dos pontos chave deste processo é a etapa de iniciação da tradução que é regulada pela ação de ao menos doze fatores protéicos chamados eIFs (eukaryotic Initiation Factor Fator de Iniciação de Eucariotos) perfazendo, aproximadamente, 30 polipeptídios em mamíferos. Os tripanossomatídeos, protozoários patogênicos de interesse médico e veterinário, apresentam características celulares próprias como a regulação da sua expressão gênica que ocorre em nível pós-transcricional. Nesse contexto a síntese de proteínas é um alvo em potencial para mecanismos de regulação, entretanto pouco se sabe sobre esse processo nos tripanossomatídeos. Em estudos prévios, foi iniciado nestes parasitas o estudo do fator eIF4F e observou-se a existência de múltiplos homólogos para cada uma de suas três subunidades. Neste trabalho utilizou-se ferramentas de bioinformática para identificar e caracterizar homólogos aos demais eIFs em Leishmania major, Trypanosoma brucei e T. cruzi. Foram identificados homólogos dos fatores eIF1, eIF1A, eIF5, eIF5A, eIF5B, eIF6 e sete subunidades do complexo eIF3 (b, c, d, e, f, i, k). Ao contrário do observado para as subunidades do eIF4F, e com a exceção da subunidade eIF3b, um único homólogo foi identificado para cada fator. A análise das seqüências protéicas mostrou que existe variabilidade no grau de conservação destes homólogos quando comparados com outros eucariotos (de 22% de identidade para o eIF3k até 58% para o eIF6). Em alguns casos foi possível mapear mutações exclusivas dos tripanossomatídeos. Também foram gerados modelos 3D de vários dos homólogos previamente identificados de subunidades do eIF4F facilitando sua caracterização funcional. Os resultados obtidos indicam que boa parte da iniciação da síntese protéica é conservada entre tripanossomatídeos e demais eucariotos. Todavia, diferenças significativas parecem ocorrer e merecem um estudo mais aprofundado Advisors/Committee Members: Pompílio de Melo Neto, Osvaldo.

Subjects/Keywords: eIF; Iniciação da Tradução; Leishamania major; Trypanosoma brucei; T. cruzi

Record Details Similar Records Cite « Share

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

APA (6^th Edition):

Katz, R. (2006). Análise computacional de candidatos a homólogos a fatores de iniciação da tradução em tripanossomatídeos. (Masters Thesis). Universidade Federal de Pernambuco. Retrieved from https://repositorio.ufpe.br/handle/123456789/6513

Chicago Manual of Style (16^th Edition):

Katz, Rodolfo. “Análise computacional de candidatos a homólogos a fatores de iniciação da tradução em tripanossomatídeos.” 2006. Masters Thesis, Universidade Federal de Pernambuco. Accessed April 12, 2021. https://repositorio.ufpe.br/handle/123456789/6513.

MLA Handbook (7^th Edition):

Katz, Rodolfo. “Análise computacional de candidatos a homólogos a fatores de iniciação da tradução em tripanossomatídeos.” 2006. Web. 12 Apr 2021.

Vancouver:

Katz R. Análise computacional de candidatos a homólogos a fatores de iniciação da tradução em tripanossomatídeos. [Internet] [Masters thesis]. Universidade Federal de Pernambuco; 2006. [cited 2021 Apr 12]. Available from: https://repositorio.ufpe.br/handle/123456789/6513.

Council of Science Editors:

Katz R. Análise computacional de candidatos a homólogos a fatores de iniciação da tradução em tripanossomatídeos. [Masters Thesis]. Universidade Federal de Pernambuco; 2006. Available from: https://repositorio.ufpe.br/handle/123456789/6513

17. Barry, Paul. The roles of cytoplasmic aspartate aminotransferase in trypanosoma brucei.

Degree: School of Biochemistry & Immunology. Discipline of Biochemistry, 2017, Trinity College Dublin

URL: http://hdl.handle.net/2262/81193

Subjects/Keywords: Aminotransferase; Indole pyruvate; indole-3-pyruvate; Indole-3-pyruvic acid; T. brucei; brucei; Trypanosomes; aromatic ketoacid; trypanosome; immune modulation; aspartate; aromatic amino acid; tryptophan; cASAT; ASAT

…1 1.1.1 T. brucei : a brief historical & evolutionary context. . . . . . . . 1 1.1.2… …T. brucei epidemiology. . . . . . . . . . . . . . . . . . . . . . . . 5 1.1.3 Life… …transamination in T. brucei. . . . . . . . . . . . . . . . . . 21 1.4.1 Alanine aminotransferase… …evasion strategies of T. brucei. . . . . . . . . . . . . . . . . . . 25 1.5.1 Antigenic… …purification of T. brucei and T. cruzi recombinant cASAT. 55 2.5.1 cASAT expression vector…

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

APA (6^th Edition):

Barry, P. (2017). The roles of cytoplasmic aspartate aminotransferase in trypanosoma brucei. (Thesis). Trinity College Dublin. Retrieved from http://hdl.handle.net/2262/81193

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Barry, Paul. “The roles of cytoplasmic aspartate aminotransferase in trypanosoma brucei.” 2017. Thesis, Trinity College Dublin. Accessed April 12, 2021. http://hdl.handle.net/2262/81193.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Barry, Paul. “The roles of cytoplasmic aspartate aminotransferase in trypanosoma brucei.” 2017. Web. 12 Apr 2021.

Vancouver:

Barry P. The roles of cytoplasmic aspartate aminotransferase in trypanosoma brucei. [Internet] [Thesis]. Trinity College Dublin; 2017. [cited 2021 Apr 12]. Available from: http://hdl.handle.net/2262/81193.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Barry P. The roles of cytoplasmic aspartate aminotransferase in trypanosoma brucei. [Thesis]. Trinity College Dublin; 2017. Available from: http://hdl.handle.net/2262/81193

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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