Sugar-assisted ligation in glycoprotein synthesis

Yu Ying Yang, Simon Ficht, Ashraf Brik, Chi Huey Wong

Research output: Contribution to journalArticlepeer-review

102 Scopus citations

Abstract

Sugar-assisted ligation (SAL) presents an attractive strategy for the synthesis of glycopeptides, including the synthesis of cysteine-free β-O-linked and N-linked glycopeptides. Here we extended the utility of SAL for the synthesis of α-O-linked glycopeptides and glycoproteins. In order to explore SAL in the context of glycoprotein synthesis, we developed a new chemical synthetic route for the α-O-linked glycoprotein diptericin ε. In the first stage of our synthesis, diptericin segment Cys(Acm) 37-Gly52 and segment Val53-Phe82 were assembled by SAL through a Gly-Val ligation junction. Subsequently, after Acm deprotection, diptericin segment Cys37-Phe82 was ligated to segment Asp1-Asn36 by means of native chemical ligation (NCL) to give the full sequence of diptericin ε. In the final synthetic step, hydrogenolysis was applied to remove the thiol handle from the sugar moiety with the concomitant conversion of mutated Cys37 into the native alanine residue. In addition, we extended the applicability of SAL to the synthesis of glycopeptides containing cysteine residues by carrying out selective desulfurization of the sulfhydryl-modified sugar moiety in the presence of acetamidomethyl (Acm) protected cysteine residues. The results presented here demonstrated for the first time that SAL could be a general and useful tool in the chemical synthesis of glycoproteins.

Original languageEnglish
Pages (from-to)7690-7701
Number of pages12
JournalJournal of the American Chemical Society
Volume129
Issue number24
DOIs
StatePublished - 20 Jun 2007

ASJC Scopus subject areas

  • Catalysis
  • Chemistry (all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint

Dive into the research topics of 'Sugar-assisted ligation in glycoprotein synthesis'. Together they form a unique fingerprint.

Cite this