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" |