Synthesis of S-alkyl L-homocysteine analogues of glutathione and their kinetic studies with gamma-glutamyl transpeptidase

Christian Lherbet; Christian Gravel; Jeffrey W Keillor

doi:10.1016/j.bmcl.2004.04.072

Synthesis of S-alkyl L-homocysteine analogues of glutathione and their kinetic studies with gamma-glutamyl transpeptidase

Bioorg Med Chem Lett. 2004 Jul 5;14(13):3451-5. doi: 10.1016/j.bmcl.2004.04.072.

Authors

Christian Lherbet¹, Christian Gravel, Jeffrey W Keillor

Affiliation

¹ Department of Chemistry, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, Que., Canada H3C 3J7.

PMID: 15177451
DOI: 10.1016/j.bmcl.2004.04.072

Abstract

A series of S-alkyl L-homocysteine analogues of glutathione was synthesized with varied oxidation state of the sulfur and tested for inhibition of rat kidney gamma-glutamyl transpeptidase (GGT). The strong selectivity of the enzyme with respect to the sulfur oxidation state reveals important information for the development of powerful competitive inhibitors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
Binding, Competitive
Crystallography, X-Ray
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Glutathione / analogs & derivatives*
Glutathione / pharmacology
Homocystine / chemical synthesis*
Homocystine / pharmacology
Kidney / metabolism
Kinetics
Methionine / analogs & derivatives*
Methionine / chemistry
Methionine / metabolism
Oxidation-Reduction
Rats
Sulfur / chemistry
Sulfur / metabolism
gamma-Glutamyltransferase / metabolism*

Substances

Enzyme Inhibitors
Homocystine
Sulfur
Methionine
gamma-Glutamyltransferase
Glutathione
methionine sulfoxide