title: Inhibition of glyoxalase I: the first low-nanomolar tight-binding inhibitors.
abstract: A series of rational modifications to the structure of known S-(N-aryl-N-hydroxycarbamoyl)glutathione-based glyoxalase I inhibitors culminated in the discovery of the first single-digit nanomolar inhibitor. This study makes available key information about possible means to address the issues of metabolic instability, low potency, and synthetic complexicity that have plagued the area of glyoxalase I inhibition. Knowledge garnered from this study has implications in the design of inhibitors with higher conformational definition and lower peptidic character.
authors.affiliation: Center for Drug Design, Academic Health Center, and Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, 8-123A Weaver Densford Hall, 308 Harvard Street SE, Minneapolis, Minnesota 55455, USA. swati.more@ucsf.edu
authors.forename: Swati S
authors.initials: SS
authors.lastname: More
authors.forename: Robert
authors.initials: R
authors.lastname: Vince
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D005723:gamma-Glutamyltransferase / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D005723:gamma-Glutamyltransferase; D007791:Lactoylglutathione Lyase