title: Peptide synthesis using unprotected peptides through orthogonal coupling methods.
abstract: We describe an approach to the synthesis of peptides from segments bearing no protecting groups through an orthogonal coupling method to capture the acyl segment as a thioester that then undergoes an intramolecular acyl transfer to the amine component with formation of a peptide bond. Two orthogonal coupling methods to give the covalent ester intermediate were achieved by either a thiol-thioester exchange mediated by a trialkylphosphine and an alkylthiol or a thioesterification by C alpha-thiocarboxylic acid reacting with a beta-bromo amino acid. With this approach, unprotected segments ranging from 4 to 37 residues were coupled to aqueous solution to give free peptides up to 54 residues long with high efficiency.
authors.affiliation: Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232-2363, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Tam
authors.forename: Y A
authors.initials: YA
authors.lastname: Lu
authors.forename: C F
authors.initials: CF
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Shao
mesh_terms: D000215:Acylation; D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D010720:Phosphines; D012996:Solutions; D013438:Sulfhydryl Compounds
chemical_list: D007202:Indicators and Reagents; D009842:Oligopeptides; D010455:Peptides; D010720:Phosphines; D012996:Solutions; D013438:Sulfhydryl Compounds; D003545:Cysteine