Toward homogeneous erythropoietin: Chemical synthesis of the Ala 1-Gly 28 glycopeptide domain by "Alanine" ligation

Cindy Kan, John D. Trzupek, Bin Wu, Qian Wan, Gong Chen, Zhongping Tan, Yu Yuan, Samuel J. Danishefsky

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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 αthioester handle, the latter feature permitting direct coupling with a glycopeptide fragment bearing N-terminal Cys 29 without further functionalization.

Original languageEnglish (US)
Pages (from-to)5438-5443
Number of pages6
JournalJournal of the American Chemical Society
Volume131
Issue number15
DOIs
Publication statusPublished - Apr 22 2009

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All Science Journal Classification (ASJC) codes

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

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