On-Resin Peptide Cyclization

摘要

Method of peptide synthesis, comprising the steps of a. synthesizing a peptide linked to a solid phase which peptide comprises at least one cysteine, homo- or nor-cysteine residue, which cysteine is protected in its side chain by a S-tert.butyl-sulphenyl group b. either coupling N-terminally a further amino acid having a 3,3'-dithio-(1-carboxy-propyl)-propionyl-radical on its Nalpha or deprotecting the Nalpha of the N-terminal amino acid and reacting the free Nalpha with 3,3'-dithio-propionic acid imide to yield the corresponding Nalpha-3,3'-dithio-(1-carboxy-propyl)-propionamide or deprotecting the Nalpha of the N-terminal amino acid and reacting the free Nalpha with a compound of formula IV R7-S-S-[CH₂]₂-COOH IV wherein R7 is aryl-, including heteronuclear aryl, or is aralkyl-, alkylaryl- or alkyl-, which may be further substituted with halogeno, amido, ester, carboxy or ether, and c. reacting the peptide with a S-tert.Butyl-sulphenyl-protection group removing reagent, and d. cyclizing the peptide by means of disulfide bond formation, preferably cyclizing the peptide in the presence of air and/or oxygen.