TY - JOUR
T1 - Synthesis and activity of γ-(L-γ-azaglutamyl)-S-(p-bromobenzyl)-L- cysteinylglycine
T2 - A metabolically stable inhibitor of glyoxalase I
AU - Vince, Robert
AU - Brownell, Jay
AU - Akella, Lakshmi B.
PY - 1999/3/22
Y1 - 1999/3/22
N2 - 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.
AB - 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.
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U2 - 10.1016/S0960-894X(99)00097-9
DO - 10.1016/S0960-894X(99)00097-9
M3 - Article
C2 - 10206549
AN - SCOPUS:0033594241
SN - 0960-894X
VL - 9
SP - 853
EP - 856
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 6
ER -