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© Institut Pasteur
Cristaux de cellulase, enzyme purifiée de Clostridium thermocellum permettant la digestion de la cellulose. Image colorisée.
Publication : Chembiochem : a European journal of chemical biology

Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Chembiochem : a European journal of chemical biology - 01 Aug 2003

Pochet S, Dugué L, Labesse G, Delepierre M, Munier-Lehmann H

Link to Pubmed [PMID] – 12898625

Chembiochem 2003 Aug;4(8):742-7

Thymidine monophosphate kinase (TMPK) from Mycobacterium tuberculosis (TMPKmt) is an attractive target for the design of specific inhibitors. This fact is the result of its key role in the thymidine pathway and of unique structural features in the active site observed by X-ray crystallography, especially in comparison to its human counterpart (TMPKh). Different 5-modified thymidine derivatives, as well as purine and pyrimidine analogues or C-nucleosides were tested on TMPKmt and TMPKh, and the results were rationalized by docking studies. 5-Halogenated 2′-deoxyuridines are the best inhibitors of TMPKmt found and present the highest selectivity indexes in favor of TMPKmt.

http://www.ncbi.nlm.nih.gov/pubmed/12898625