New disulfide bond-forming reactions for peptide and protein synthesis.
1. In order to solve the difficult problems for the synthesis of peptides or proteins containing several disulfide bonds, three new disulfide bond-forming reactions were developed. 2. Thallium(III) trifluoroacetate oxidation. This reagent, a mild oxidant with a soft acid character, cleaved various S-protecting groups of cysteine in trifluoroacetic acid, with spontaneous formation of cystine. Thus, some model peptides containing a disulfide bond were prepared by direct oxidative conversion of the respective S-substituted cysteine peptides. 3. Sulfoxide-directed disulfide bond-forming reaction. The disulfide bond was formed at the sulfur atom of Cys(R)(O) (sulfoxide) intermolecularly as well as intramolecularly following liberation of the SH group from the coreactant, Cys(R'), by a suitable acid. Thus, formation of the disulfide bond was found to be feasible at the position of Cys(R)(O). 4. Silylchloride-sulfoxide procedure. In the presence of diphenylsulfoxide, methyltrichlorosilane in trifluoroacetic acid cleaved various S-protecting groups to form cystine within 10 to 30 min at 4 degrees C. By combination of this new disulfide bond-forming reaction and others, some peptides containing two or three disulfide bonds were synthesized successfully.
Kiso
Y
Y
Kyoto Pharmaceutical University, Japan.
Fujii
N
N
Yajima
H
H
D000595:Amino Acid Sequence; D000818:Animals; D004220:Disulfides / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010452:Peptide Biosynthesis; D013454:Sulfoxides / Q000378:metabolism*
D004220:Disulfides; D013454:Sulfoxides