S-fluorenylmethoxycarbonyl glutathione and diesters: inhibition of mammalian glyoxalase II.

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Chyan MK, Elia AC, Principato GB, Giovannini E, Rosi G, Norton SJ

S-fluorenylmethoxycarbonyl glutathione and diesters: inhibition of mammalian glyoxalase II.

Enzyme Protein. 1994-1995;48(3):164-73.

PubMed ID

8589803 [ View in PubMed

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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 (Ki = 2.1 mumol/l). Inhibition constants (Ki 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 mumol/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 mumol/l. Diesters of FMOC-G may be useful in studies of the glyoxalase enzyme system in cultured mammalian cells.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Glutathione	Hydroxyacylglutathione hydrolase, mitochondrial	Protein	Humans	Unknown	Not Available	Details