N,S-bis-fluorenylmethoxycarbonylglutathione: a new, very potent inhibitor of mammalian glyoxalase II.

Abstract

A very potent competitive inhibitor of mammalian glyoxalase II activity, N,S-bis-fluorenylmethoxycarbonylglutathione (DiFMOC-G) has been synthesized and characterized. The Ki value for inhibition of glyoxalase II purified from calf liver is 0.08 microM. The Ki values for glyoxalase I inhibitions range from 285 to 500 fold higher than the values obtained for glyoxalase II inhibitions, depending on the source of the enzyme. Among other enzymes involved in glutathione metabolism, such as glutathione S-transferase, glutathione reductase, and glutathione peroxidase, only glutathione S-transferase is inhibited to a small extent by DiFMOC-G. Diesters of DiFMOC-G were prepared in order to improve transport of DiFMOC-G into mammalian tumor cells (rat adrenal pheochromocytoma, PC-12) in culture. Among the diesters synthesized, diisopropyl DiFMOC-G was found to be the most inhibitory to cell viability, with a [I]0.5 value of 3 microM.

• Authors: A C Elia, M K Chyan, G B Principato, E Giovannini, G Rosi, S J Norton
• Journal: Biochemistry and molecular biology international (Biochem Mol Biol Int) Vol. 35 Issue 4 Pg. 763-71 (Apr 1995) ISSN: 1039-9712 [Print] England
• PMID: 7627127 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Fluorenes
• N,S-bis-fluorenylmethoxycarbonylglutathione
• Glutathione Peroxidase
• Glutathione Reductase
• Glutathione Transferase
• Thiolester Hydrolases
• hydroxyacylglutathione hydrolase
• Lactoylglutathione Lyase
• Glutathione

Topics

• Animals
• Binding, Competitive
• Biological Transport
• Cattle
• Enzyme Inhibitors (pharmacology)
• Fluorenes (isolation & purification, pharmacology)
• Glutathione (analogs & derivatives, isolation & purification, pharmacology)
• Glutathione Peroxidase (antagonists & inhibitors, metabolism)
• Glutathione Reductase (antagonists & inhibitors, metabolism)
• Glutathione Transferase (antagonists & inhibitors, metabolism)
• Kinetics
• Lactoylglutathione Lyase (antagonists & inhibitors, metabolism)
• Rats
• Thiolester Hydrolases (antagonists & inhibitors, metabolism)
• Tumor Cells, Cultured