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Comparative Study of Purine and Pyrimidine Nucleoside Analogues Acting on the Thymidylate Kinases of Mycobacterium tuberculosis and of Humans
Author(s) -
Pochet Sylvie,
Dugué Laurence,
Labesse Gilles,
Delepierre Muriel,
MunierLehmann Hélène
Publication year - 2003
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200300608
Subject(s) - nucleoside , pyrimidine , thymidine , purine , thymidine kinase , nucleotide salvage , mycobacterium tuberculosis , docking (animal) , kinase , chemistry , biochemistry , thymidylate synthase , enzyme , stereochemistry , nucleotide , biology , tuberculosis , dna , virology , gene , medicine , genetics , cancer , virus , fluorouracil , nursing , pathology , herpes simplex virus
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.