title: Native Chemical Ligation Strategy to Overcome Side Reactions during Fmoc-Based Synthesis of C-Terminal Cysteine-Containing Peptides.
abstract: The Fmoc-based solid phase synthesis of C-terminal cysteine-containing peptides is problematic, due to side reactions provoked by the pronounced acidity of the Cα proton of cysteine esters. We herein describe a general strategy consisting of the postsynthetic introduction of the C-terminal Cys through a key chemoselective native chemical ligation reaction with N-Hnb-Cys peptide crypto-thioesters. This method was successfully applied to the demanding peptide sequences of two natural products of biological interest, giving remarkably high overall yields compared to that of a state of the art strategy.
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Lelièvre
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Victor P
authors.initials: VP
authors.lastname: Terrier
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Agnès F
authors.initials: AF
authors.lastname: Delmas
authors.affiliation: Centre de Biophysique Moléculaire, CNRS UPR 4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Aucagne
mesh_terms: D003545:Cysteine / Q000138:chemical synthesis* / Q000737:chemistry; D008026:Ligation; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D010455:Peptides; D003545:Cysteine