Abstract
The design, synthesis, and enzyme kinetics evaluation of a transition-state inhibitor of glyoxalase-I is described. The union of the hydroxamic acid zinc-chelator with a urea isostere for the glu-cys amide bond led to a glutathione analog which retained inhibitory potency toward glyoxalase-I while possessing resistance toward γ-glutamyltranspeptidase mediated breakdown. This compound is viewed as a potential lead for the development of second-generation glyoxalase-I inhibitors wherein, the problems pertaining to metabolism and selectivity are overcome.
Original language | English (US) |
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Pages (from-to) | 6039-6042 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 16 |
Issue number | 23 |
DOIs | |
State | Published - Dec 1 2006 |
Bibliographical note
Copyright:Copyright 2008 Elsevier B.V., All rights reserved.
Keywords
- Glutathione
- Glyoxalase
- Hydroxamic acid
- Methylglyoxal
- Transition-state inhibitor
- γ-Glutamyltranspeptidase