Glutathione. 13. Mechanism of Thiol Oxidation by Diazenedicarboxylic Acid Derivatives

Edward M. Kosower, Hanna Kanety-Londner

Research output: Contribution to journalArticlepeer-review

Abstract

Kinetic, spectroscopic, and product studies on the reaction of the tripeptide thiol, glutathione (GSH), with the diazenedicarboxylic acid bisamides, X(CH2CH2)2NCON=NCON(CH2CH2)2X, with X = NCH3 (DIP), X = N(CH3)2+ (DIP+2), X = O (MOR), X = CH2 (PIP), etc., revealed two distinguishable stages: (a) GSH + YN=NY → YN(SG)NHY; (b) GSH + YN(SG)NHY → GSSG + YNHNHY. The rate of disappearance of diazene (stage a) increased greatly as X changed from CH2 to N(CH3)2+; the rate of disappearance of intermediate (stage b) also increased greatly for the same change in substitution but not as much as the rate for stage a. Hydrolysis rates for the diazene derivatives paralleled the rates for thiol oxidation. Hydrolysis of DIP between pH 10.2 and 10.9 generated the monoacyldiazenecarboxylate ion CH3N(CH2CH2)2NCON=NCOO-, which gave rise to N-formyl-N′-methylpiperazine, N-methylpiperazine, N2, and CO2 on further hydrolysis. The s-cis conformation is assigned to the diazenedicarboxylic acid bisamides.

Original languageEnglish
Pages (from-to)3001-3007
Number of pages7
JournalJournal of the American Chemical Society
Volume98
Issue number10
DOIs
StatePublished - 1 May 1976

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