TY - JOUR
T1 - Glutathione. 13. Mechanism of Thiol Oxidation by Diazenedicarboxylic Acid Derivatives
AU - Kosower, Edward M.
AU - Kanety-Londner, Hanna
PY - 1976/5/1
Y1 - 1976/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0017305034&partnerID=8YFLogxK
U2 - 10.1021/ja00426a054
DO - 10.1021/ja00426a054
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AN - SCOPUS:0017305034
VL - 98
SP - 3001
EP - 3007
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 10
ER -