Inhibitors having high specificity toward mammalian glyoxalase II, but not glyoxalase I, were sought as part of a program to study glyoxalase enzyme function in mammalian cells. The compound, S-fluorenylmethoxycarbonyl glutathione (FMOC-G), was synthesized and found to be a competitive inhibitor of purified calf liver glyoxalase II (K-i = 2.1 mu mol/l). Inhibition constants (K-i values) for the other glyoxalase enzyme, glyoxalase I, and the glutathione-requiring enzyme, glutathione S-transferase, from other sources, were found to be 17 and 25 mu mol/l, respectively. FMOC-G is a very poor inhibitor of glutathione reductase and glutathione peroxidase. Diesters (dimethyl, diethyl, diisopropyl) of FMCO-G were also synthesized, as proinhibitors, to improve transport of FMOC-G into mammalian tumor cells (rat adrenal pheochromocytoma, PC-12) in culture. The diesters were inhibitory to cell growth and variability; the most effective of these, diisopropyl FMOC-G, exhibited an [I](0.5) value of approximately 275 mu mol/l. Diesters of FMOC-G may be useful in studies of the glyoxalase enzyme system in cultured mammalian cells.
S-Fluorenylmethoxycarbonylglutathione and diesters: inhibition of mammalian glyoxalase II
ELIA A. C.;PRINCIPATO G.;GIOVANNINI E.;G. ROSI;
1995
Abstract
Inhibitors having high specificity toward mammalian glyoxalase II, but not glyoxalase I, were sought as part of a program to study glyoxalase enzyme function in mammalian cells. The compound, S-fluorenylmethoxycarbonyl glutathione (FMOC-G), was synthesized and found to be a competitive inhibitor of purified calf liver glyoxalase II (K-i = 2.1 mu mol/l). Inhibition constants (K-i values) for the other glyoxalase enzyme, glyoxalase I, and the glutathione-requiring enzyme, glutathione S-transferase, from other sources, were found to be 17 and 25 mu mol/l, respectively. FMOC-G is a very poor inhibitor of glutathione reductase and glutathione peroxidase. Diesters (dimethyl, diethyl, diisopropyl) of FMCO-G were also synthesized, as proinhibitors, to improve transport of FMOC-G into mammalian tumor cells (rat adrenal pheochromocytoma, PC-12) in culture. The diesters were inhibitory to cell growth and variability; the most effective of these, diisopropyl FMOC-G, exhibited an [I](0.5) value of approximately 275 mu mol/l. Diesters of FMOC-G may be useful in studies of the glyoxalase enzyme system in cultured mammalian cells.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
