Document Detail

Reversible and Efficient Inhibition of UDP-Galactopyranose Mutase by Electrophilic, Constrained and Unsaturated UDP-Galactitol Analogues.
MedLine Citation:
PMID:  23015271     Owner:  NLM     Status:  Publisher    
A series of UDP-galactitols were designed as analogues of high-energy intermediates of the UDP-galactopyranose mutase (UGM) catalyzed furanose/pyranose interconversion, an essential step of Mycobacterium tuberculosis cell wall biosynthesis. The final compounds structurally share the UDP and the galactitol substructures that were connected by four distinct electrophilic connections (epoxide, lactone and Michael acceptors). All molecules were synthesized from a common perbenzylated acyclic galactose precursor that was derivatized by alkenylation, alkynylation and cyclopropanation. The inhibition study against UGM could clearly show that slight changes in the relative orientation of the UDP and the galactitol moieties resulted in dramatic variations of binding properties. Compared to known inhibitors, the epoxide derivative displayed a very tight, reversible, inhibition profile. Moreover, a time-dependent inactivation study showed that none of these electrophilic structures could react with UGM, or its FAD cofactor, the catalytic nucleophile of this still intriguing reaction.
Christophe Ansiaux; Inès N'go; Stéphane P Vincent
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-27
Journal Detail:
Title:  Chemistry (Weinheim an der Bergstrasse, Germany)     Volume:  -     ISSN:  1521-3765     ISO Abbreviation:  Chemistry     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9513783     Medline TA:  Chemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Département de Chimie, Laboratoire de Chimie Bio-Organique, University of Namur (FUNDP), Académie Louvain rue de Bruxelles 61, 5000 Namur (Belgium), Fax: (+32) 81-72-45-17.
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