title: Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation.
abstract: The Ala(1)-Gly(28) glycopeptide fragment (28) of EPO was prepared by chemical synthesis as a single glycoform. Key steps in the synthesis include attachment of a complex dodecasaccharide (7) to a seven amino acid peptide via Lansbury aspartylation, native chemical ligation to join peptide 19 with the glycopeptide domain 18, and a selective desulfurization at the ligation site to reveal the natural Ala(19). This glycopeptide fragment (28) contains both the requisite N-linked dodecasaccharide and a C-terminal (alpha)thioester handle, the latter feature permitting direct coupling with a glycopeptide fragment bearing N-terminal Cys(29) without further functionalization.
authors.affiliation: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Kan
authors.forename: John D
authors.initials: JD
authors.lastname: Trzupek
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Qian
authors.initials: Q
authors.lastname: Wan
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Tan
authors.forename: Yu
authors.initials: Y
authors.lastname: Yuan
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky