Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation

J Am Chem Soc. 2009 Apr 22;131(15):5438-43. doi: 10.1021/ja808707w.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alanine / chemistry*
  • Erythropoietin / chemical synthesis*
  • Glycopeptides / chemical synthesis*
  • Glycosylation
  • Peptide Fragments / chemical synthesis*
  • Polysaccharides
  • Protein Structure, Tertiary

Substances

  • Glycopeptides
  • Peptide Fragments
  • Polysaccharides
  • Erythropoietin
  • Alanine