Disulfide bond-forming reaction using a dimethyl sulfoxide/aqueous HCl system and its application to regioselective two disulfide bond formation.
Disulfide bond formation in S-acetamidomethyl (Acm) cysteine-containing peptides by successive treatments with silver trifluoromethanesulfonate (AgOTf) and dimethyl sulfoxide (DMSO)/aqueous HCl is described. An S-Acm cysteine was found to be quantitatively converted into cysteine by deprotection of the Acm group with AgOTf followed by DMSO/aqueous HCl treatment. Under these reaction conditions, no significant side reactions were observed with oxidation-sensitive amino acids such as Met, Tyr and Trp. Oxytocin and a Trp-containing peptide, urotensin II, were prepared by this method. Furthermore, regioselective two disulfide bond formation was found to be feasible by the combination of air oxidation and the AgOTf-DMSO/HCl system. This strategy has been successfully applied to the syntheses of tachyplesin I and endothelin I, which have two disulfide bonds and a Trp residue in the molecule.
Tamamura
H
H
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Otaka
A
A
Nakamura
J
J
Okubo
K
K
Koide
T
T
Ikeda
K
K
Ibuka
T
T
Fujii
N
N
D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000031:analogs & derivatives / Q000737:chemistry; D003553:Cystine / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000138:chemical synthesis / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D016232:Endothelins / Q000138:chemical synthesis / Q000737:chemistry; D006851:Hydrochloric Acid / Q000737:chemistry; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010121:Oxytocin / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry; D018030:Silver Compounds / Q000737:chemistry; D014579:Urotensins / Q000138:chemical synthesis / Q000737:chemistry
D023181:Antimicrobial Cationic Peptides; D004268:DNA-Binding Proteins; D004220:Disulfides; D016232:Endothelins; D010455:Peptides; D010456:Peptides, Cyclic; D018030:Silver Compounds; D014579:Urotensins; C057636:tachyplesin peptide, Tachypleus tridentatus; D003553:Cystine; D010121:Oxytocin; C029677:urotensin II; D003545:Cysteine; D006851:Hydrochloric Acid; D004121:Dimethyl Sulfoxide