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.
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Authors | M K Chyan, A C Elia, G B Principato, E Giovannini, G Rosi, S J Norton |
Journal | Enzyme & protein
(Enzyme Protein)
1994-1995
Vol. 48
Issue 3
Pg. 164-73
ISSN: 1019-6773 [Print] Switzerland |
PMID | 8589803
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Inhibitors
- Esters
- Fluorenes
- S-fluorenylmethoxycarbonylglutathione
- Glutathione Peroxidase
- Glutathione Reductase
- Glutathione Transferase
- Thiolester Hydrolases
- hydroxyacylglutathione hydrolase
- Lactoylglutathione Lyase
- Glutathione
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Topics |
- Animals
- Cattle
- Cell Division
(drug effects)
- Cell Survival
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Esters
- Fluorenes
(chemical synthesis, pharmacology)
- Glutathione
(analogs & derivatives, chemical synthesis, pharmacology)
- Glutathione Peroxidase
(metabolism)
- Glutathione Reductase
(metabolism)
- Glutathione Transferase
(metabolism)
- Kinetics
- Lactoylglutathione Lyase
(antagonists & inhibitors, metabolism)
- Liver
(enzymology)
- Magnetic Resonance Spectroscopy
- PC12 Cells
- Rats
- Thiolester Hydrolases
(antagonists & inhibitors, metabolism)
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