title: Synthesis of peptide alkylthioesters using the intramolecular N,S-acyl shift properties of bis(2-sulfanylethyl)amido peptides.
abstract: The design of novel methods giving access to peptide alkylthioesters, the key building blocks for protein synthesis using Native Chemical Ligation, is an important area of research. Bis(2-sulfanylethyl)amido peptides (SEA peptides) 1 equilibrate in aqueous solution with S-2-(2-mercaptoethylamino)ethyl thioester peptides 2 through an N,S-acyl shift mechanism. HPLC was used to study the rate of equilibration for different C-terminal amino acids and the position of equilibrium as a function of pH. We show also that thioester form 2 can participate efficiently in a thiol-thioester exchange reaction with 5% aqueous 3-mercaptopropionic acid. The highest reaction rate was obtained at pH 4. These experimental conditions are significantly less acidic than those reported in the past for related systems. The method was validated with the synthesis of a 24-mer peptide thioester. Consequently, SEA peptides 1 constitute a powerful platform for access to native chemical ligation methodologies.
authors.affiliation: CNRS UMR 8161, Université Lille Nord de France, Institut Pasteur de Lille, IFR 142, 1 rue du Pr Calmette, 59021 Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dheur
authors.forename: Nathalie
authors.initials: N
authors.lastname: Ollivier
authors.forename: Aurélie
authors.initials: A
authors.lastname: Vallin
authors.forename: Oleg
authors.initials: O
authors.lastname: Melnyk
mesh_terms: D000215:Acylation; D000577:Amides / Q000737:chemistry*; D000595:Amino Acid Sequence; D004952:Esters; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D000577:Amides; D004952:Esters; D010455:Peptides