945979-59-9Relevant academic research and scientific papers
Design, synthesis, and binding studies of bidentate Zn-chelating peptidic inhibitors of glyoxalase-I
More, Swati S.,Vince, Robert
, p. 3793 - 3797 (2007)
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 β-keto ester compounds are reported.
Inhibition of glyoxalase I: The first low-nanomolar tight-binding inhibitors
More, Swati S.,Vince, Robert
supporting information; experimental part, p. 4650 - 4656 (2010/03/01)
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.
