Literature DB >> 25049244

Drug target identification using a trypanosome overexpression library.

Daniela Begolo1, Esteban Erben2, Christine Clayton1.   

Abstract

Elucidation of molecular targets is very important for lead optimization during the drug development process. We describe a direct method to find targets of antitrypanosomal compounds against Trypanosoma brucei using a trypanosome overexpression library. As proof of concept, we treated the library with difluoromethylornithine and DDD85646 and identified their respective targets, ornithine decarboxylase and N-myristoyltransferase. The overexpression library could be a useful tool to study the modes of action of novel antitrypanosomal drug candidates.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.

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Year:  2014        PMID： 25049244      PMCID： PMC4187942          DOI： 10.1128/AAC.03338-14

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN： 0066-4804            Impact factor:   5.191


  26 in total

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Journal:  Exp Parasitol       Date:  1997-11       Impact factor: 2.011

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Authors:  S Biebinger; L E Wirtz; P Lorenz; C Clayton
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Authors:  H Hirumi; K Hirumi
Journal:  J Parasitol       Date:  1989-12       Impact factor: 1.276

4.  X-ray structure of ornithine decarboxylase from Trypanosoma brucei: the native structure and the structure in complex with alpha-difluoromethylornithine.

Authors:  N V Grishin; A L Osterman; H B Brooks; M A Phillips; E J Goldsmith
Journal:  Biochemistry       Date:  1999-11-16       Impact factor: 3.162

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Authors:  J A Coderre; S M Beverley; R T Schimke; D V Santi
Journal:  Proc Natl Acad Sci U S A       Date:  1983-04       Impact factor: 11.205

6.  Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids.

Authors:  A H Fairlamb; P Blackburn; P Ulrich; B T Chait; A Cerami
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7.  Unstable amplification of two extrachromosomal elements in alpha-difluoromethylornithine-resistant Leishmania donovani.

Authors:  S Hanson; S M Beverley; W Wagner; B Ullman
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8.  Site-specific DNA double-strand breaks greatly increase stable transformation efficiency in Trypanosoma brucei.

Authors:  Lucy Glover; David Horn
Journal:  Mol Biochem Parasitol       Date:  2009-08       Impact factor: 1.759

9.  Myristoyl-CoA:protein N-myristoyltransferase depletion in trypanosomes causes avirulence and endocytic defects.

Authors:  Helen P Price; M Lucia S Güther; Michael A J Ferguson; Deborah F Smith
Journal:  Mol Biochem Parasitol       Date:  2009-09-24       Impact factor: 1.759

10.  A genome-wide tethering screen reveals novel potential post-transcriptional regulators in Trypanosoma brucei.

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Review 5.  Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.

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Journal:  Microorganisms       Date:  2020-06-24

6.  Mapping the metabolism of five amino acids in bloodstream form Trypanosoma brucei using U-13C-labelled substrates and LC-MS.

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7.  Clinical and veterinary trypanocidal benzoxaboroles target CPSF3.

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Review 8.  Drug resistance in eukaryotic microorganisms.

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Journal:  Nat Microbiol       Date:  2016-06-24       Impact factor: 17.745

Review 9.  Genetically Validated Drug Targets in Leishmania: Current Knowledge and Future Prospects.

Authors:  Nathaniel G Jones; Carolina M C Catta-Preta; Ana Paula C A Lima; Jeremy C Mottram
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