PEPTIDE-SYNTHESIS USING UNPROTECTED PEPTIDES THROUGH ORTHOGONAL COUPLING METHODS

We describe an approach to the synthesis of peptides from segments bea ring no protecting groups through an orthogonal coupling method to cap ture the acyl segment as a thioester that then undergoes an intramolec ular acyl transfer to the amine component with formation of a peptide bond. Two orthogonal coupling methods to give the covalent ester inter mediate were achieved by either a thiol-thioester exchange mediated by a trialkylphosphine and an alkylthiol or a thioesterification by C-al pha-thiocarboxylic acid reacting with a beta-bromo amino acid. With th is approach, unprotected segments ranging from 4 to 37 residues were c oupled in aqueous solution to give free peptides up to 54 residues lon g with high efficiency.