Syntheses and kinetic evaluation of hydroxamate-based peptide inhibitors of glyoxalase I.
Hydroxamate-containing tripeptide analogs resembling a reactive intermediate in glyoxalase I catalysis were prepared by solution methods and were found to be competitive inhibitors of the enzyme from Saccharomyces cerevisiae. Electronic properties of the hydroxamate functionality as well as those of the expected intermediates in the enzyme-catalyzed reaction were compared.
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Department of Chemistry, University of Waterloo, Ontario, Canada.
Clugston
S L
SL
Sampson
P B
PB
Honek
J F
JF
D001667:Binding, Competitive; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016339:Spectrometry, Mass, Fast Atom Bombardment
D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007202:Indicators and Reagents; D009842:Oligopeptides; D007791:Lactoylglutathione Lyase