Synthesis and Kinetic Evaluation of S-and N-Substituted Cysteinylglycines as Inhibitors of Glyoxalase I

Eight S-and N-substituted L-cysteinylglycines were prepared by condensation of S-benzyl-L-cysteinylglycine or S-(p-bromobenzyl)-L-cysteinylglycine with glutaric anhydride, succinic anhydride, or the appropriately blocked and activated amino acids. In contrast to the previously prepared S-substituted glutathiones, all of the title compounds exhibited noncompetitive inhibition of yeast glyoxalase I. A kinetic evaluation under Yonetani-Thorell conditions established the existence of two binding sites on the glyoxalase I enzyme.