Toward homogeneous erythropoietin: Fine tuning of the C-terminal acyl donor in the chemical synthesis of the Cys 29-Gly 77 glycopeptide domain

Yu Yuan, Jin Chen, Qian Wan, Zhongping Tan, Gong Chen, Cindy Kan, Samuel J. Danishefsky

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Described herein is the chemical synthesis of the Cys 29-Gly 77 glycopeptide domain (22) of erythropoietin. Our initial ligation strategy targeted a C → N termini condensation between glycopeptide 3 and peptide 4. However, the reaction was hindered by the "unattainable" reactivity, mismatched polarity, and severe aggregation of the (glyco)peptide substrates. In contrast, by tuning the C-terminal acyl donor and using smaller peptide fragments, the Cys 29-Gly 77 glycopeptide domain of erythropoietin was prepared through unconventional N → C termini condensation reactions. The use of a p-cyanonitrophenyl ester and the development of a masked thiophenyl ester as acyl donors enabled us to promptly access glycopeptides bearing complex carbohydrates and offer potential synthetic applications beyond our current work.

Original languageEnglish (US)
Pages (from-to)5432-5437
Number of pages6
JournalJournal of the American Chemical Society
Volume131
Issue number15
DOIs
StatePublished - Apr 22 2009

All Science Journal Classification (ASJC) codes

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

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