Design, synthesis, and binding studies of bidentate Zn-chelating peptidic inhibitors of glyoxalase-I

Swati S More; Robert Vince

doi:10.1016/j.bmcl.2006.12.056

Design, synthesis, and binding studies of bidentate Zn-chelating peptidic inhibitors of glyoxalase-I

Bioorg Med Chem Lett. 2007 Jul 1;17(13):3793-7. doi: 10.1016/j.bmcl.2006.12.056. Epub 2006 Dec 21.

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, Minneapolis, MN 55455, USA.

PMID: 17513107
DOI: 10.1016/j.bmcl.2006.12.056

Abstract

The known affinity of ethyl acetoacetate (ACC) toward divalent zinc prompted us to attempt its employment as a chelating moiety in the design of glyoxalase-I inhibitors. A practical synthetic route was developed to incorporate this pharmacophore into the side chain of glutamic acid, with flexibility to allow incorporation of additional functionality at the end-stage of the synthesis. Herein, the details of this synthetic approach as well as the evaluation of the resultant beta-keto ester compounds are reported.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Chelating Agents / chemistry
Chelating Agents / pharmacology*
Chemistry, Pharmaceutical / methods
Crystallography, X-Ray
Drug Design
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Glutamic Acid / chemistry
Hydrogen Bonding
Kinetics
Lactoylglutathione Lyase / antagonists & inhibitors*
Lactoylglutathione Lyase / chemistry*
Ligands
Models, Chemical
Oxygen / chemistry
Peptides / chemistry
Zinc / chemistry*

Substances

Chelating Agents
Enzyme Inhibitors
Ligands
Peptides
Glutamic Acid
Lactoylglutathione Lyase
Zinc
Oxygen