Synthesis and activity of γ-(L-γ-azaglutamyl)-S-(p-bromobenzyl)-L- cysteinylglycine: A metabolically stable inhibitor of glyoxalase I

Robert Vince, Jay Brownell, Lakshmi B. Akella

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Abstract

The inhibition of glyoxalase I enzyme to increase cellular levels of methylglyoxal has been developed as a rationale for the production of anticancer agents. Synthesis of a peptidomimetic analog of the previously prepared potent glyoxalase inhibitor, S-(p-bromobenzyl)glutathione (PBBG), was accomplished by inserting a urea linkage, NH-CO-NH, to replace the γ- glutamyl peptide bond. Thus, the target compound, γ-(L-γ-azaglutamyl)-S- (p-bromobenzyl)-L-cysteinylglycine 6, was a potent inhibitor of glyoxalase I with almost no loss of activity when compared to PBBG. However, unlike PBBG, 6 was completely resistant to enzymatic degradation by kidney homogenate or by purified γ-glutamyltranspeptidase enzyme.

Original languageEnglish (US)
Pages (from-to)853-856
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume9
Issue number6
DOIs
StatePublished - Mar 22 1999

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