Protected peptide disulfides by oxidative detachment from a support.
A new and efficient procedure for the preparation of protected cyclized and protected symmetrical dimeric peptide disulfides is described. A thiol is immobilized onto a solid phase through coupling of the thiol function with a resin-linked trityl group. Following conventional peptide assembly using the Fmoc-strategy, detachment is performed by oxidation with iodine in a suitable organic solvent. When N,N-dimethylformamide is used as the solvent, and the peptide chain contains an acetamidomethylthio function, located N-terminally in a N alpha-(9-fluorenylmethyloxycarbonyl), or N alpha-tert-butyloxycarbonyl cysteinyl residue, or occurring in the chain, then the corresponding fully protected cyclic peptide disulfide will be obtained in high yield and purity. In other solvents (e.g. dioxane or chloroform-methanol 1:1, v/v), the iodine-mediated oxidation gave not only the cyclic product, but also substantial amounts of the parallel symmetrical dimeric peptide retaining Cys(Acm) at the two identical N-termini.
Rietman
B H
BH
Laboratory of Organic Chemistry, Catholic University, Nijmegen, The Netherlands.
Smulders
R H
RH
Eggen
I F
IF
van Vliet
A
A
van de Werken
G
G
Tesser
G I
GI
D000595:Amino Acid Sequence; D004126:Dimethylformamide; D004220:Disulfides / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis*; D012997:Solvents
D004220:Disulfides; D007202:Indicators and Reagents; D010455:Peptides; D012997:Solvents; D004126:Dimethylformamide