A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I

Swati S More; Robert Vince

doi:10.1016/j.bmcl.2006.08.121

A metabolically stable tight-binding transition-state inhibitor of glyoxalase-I

Bioorg Med Chem Lett. 2006 Dec 1;16(23):6039-42. doi: 10.1016/j.bmcl.2006.08.121. Epub 2006 Sep 25.

Authors

Swati S More¹, Robert Vince

Affiliation

¹ Center for Drug Design, Academic Health Center, and Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 8-123A WDH, 308 Harvard St SE, Minneapolis, MN 55455, USA.

PMID: 16997560
DOI: 10.1016/j.bmcl.2006.08.121

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 gamma-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.

MeSH terms

Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / metabolism*
Glutathione / metabolism
Lactoylglutathione Lyase / antagonists & inhibitors*
Lactoylglutathione Lyase / metabolism*
Molecular Structure
Protein Binding

Substances

Enzyme Inhibitors
Lactoylglutathione Lyase
Glutathione