title: An efficient solid-phase synthesis of peptidyl-N-acetylguanidines for use in native chemical ligation.
abstract: In the modern protocols of chemical protein syntheses, peptide-α-thioesters have been used as key components for the assembly of full-length polypeptides through chemoselective peptide coupling reactions. A variety of thioester precursors have been developed for the synthesis of the peptide-α-thioesters by Fmoc solid phase peptide synthesis (Fmoc-SPPS). Recently our group found a peptidyl-N-acetylguanidine as a new peptide-α-thioester precursor. This peptide derivative can be converted into a corresponding peptide-α-thioester only by treatment with an excess amount of a thiol in aqueous buffers at around neutral pH. This unique property allowed us to envision the practical use of the peptidyl-N-acetylguanidines for the chemical syntheses of proteins; however, an efficient synthetic method has been lacking. Herein, we report an efficient solid-phase synthesis of peptidyl-N-acetylguanidines. This new synthetic method employing selective activation and cleavage of a peptide bond successfully provided peptidyl-N-acetylguanidines from the on-resin protected peptides prepared by standard Fmoc-SPPS. We also evaluated the reactivity of a peptidyl-N-acetylguanidine in native chemical ligation through the synthesis of glucose-dependent insulinotropic polypeptide analogue. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Graduate School of Science, Department of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Okamoto
authors.affiliation: Graduate School of Science, Department of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Isoe
authors.affiliation: Graduate School of Science, Department of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Izumi
authors.affiliation: Graduate School of Science, Department of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kajihara
mesh_terms: D004952:Esters / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*
chemical_list: D004952:Esters; D010455:Peptides
keywords: chemical protein synthesis; native chemical ligation; peptide-α-thioester; peptidyl-N-acetylguanidine; thioester precursor