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


Authors: Kan, C.; Trzupek, J. D.; Wu, B.; Wan, Q.; Chen, G.; Tan, Z.; Yuan, Y.; Danishefsky, S. J.
Article Title: Toward homogeneous erythropoietin: Chemical synthesis of the Ala (1)-Gly(28) 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 (α)thioester handle, the latter feature permitting direct coupling with a glycopeptide fragment bearing N-terminal Cys(29) without further functionalization. © 2009 American Chemical Society.
Keywords: protein domain; erythropoietin; carboxy terminal sequence; chemistry; amines; amino terminal sequence; protein synthesis; peptide fragments; peptide fragment; glycosylation; protein structure, tertiary; polysaccharide; alanine; amino acids; organic acids; protein structure; polysaccharides; protein tertiary structure; synthesis; synthesis (chemical); glycopeptide; glycopeptides; chemical synthesis; desulfurization; cysteine; amino acid peptides; direct coupling; functionalization; glycoform; n-linked; n-terminal; native chemical ligation; thioester; carbohydrate; carboxy terminal telopeptide; glycine; nitrogen; chemical procedures
Journal Title: Journal of the American Chemical Society
Volume: 131
Issue: 15
ISSN: 0002-7863
Publisher: American Chemical Society  
Date Published: 2009-04-22
Start Page: 5438
End Page: 5443
Language: English
DOI: 10.1021/ja808707w
PUBMED: 19334679
PROVIDER: scopus
PMCID: PMC2765573
DOI/URL:
Notes: --- - "Cited By (since 1996): 12" - "Export Date: 30 November 2010" - "CODEN: JACSA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Bin Wu
    8 Wu
  2. Qian Wan
    23 Wan
  3. Gong Chen
    12 Chen
  4. Yu Yuan
    11 Yuan
  5. Cindy Kan
    7 Kan
  6. Zhongping Tan
    15 Tan