title: Convenient synthesis of a sialylglycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide.
abstract: Access to glycopeptides with C-terminal thioester functionality is essential for the synthesis of large glycopeptides and glycoproteins through the use of native chemical ligation. Toward that end, we have developed a concise method for the synthesis of a glycopeptide thioester having an intact complex-type dibranched disialyl-oligosaccharide. The synthesis employed a coupling reaction between benzylthiol and a free carboxylic acid at the C-terminus of a glycopeptide in which the peptide side chains are protected. After construction of glycopeptide on the HMPB-PEGA resin through the Fmoc-strategy, the protected glycopeptide was released upon treatment with acetic acid/trifluoroethanol and then the C-terminal carboxylic acid was coupled with benzylthiol at -20 degrees C in DMF. For this coupling, PyBOP/DIPEA was found to be the best for the formation of the thioester, while avoiding racemization. Finally, the protecting groups were removed in good yield with 95% TFA, thus affording a glycopeptide-thioester having an intact and homogeneous complex-type disialyl-oligosaccharide.
authors.affiliation: International Graduate School of Arts and Sciences, Yokohama City University, 22-2, Seto, Yokohama 236-0027, Japan. kajihara@yokohama-cu.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kajihara
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshihara
authors.forename: Kiriko
authors.initials: K
authors.lastname: Hirano
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D006020:Glycopeptides / Q000138:chemical synthesis*; D009844:Oligosaccharides / Q000138:chemical synthesis*; D012794:Sialic Acids / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000138:chemical synthesis
chemical_list: D006020:Glycopeptides; D009844:Oligosaccharides; D012794:Sialic Acids; D013457:Sulfur Compounds