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Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 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 (alpha)thioester handle, the latter feature permitting direct coupling with a glycopeptide fragment bearing N-terminal Cys(29) without further functionalization.

SUBMITTER: Kan C

PROVIDER: S-EPMC2765573 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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

Kan Cindy C Trzupek John D JD Wu Bin B Wan Qian Q Chen Gong G Tan Zhongping Z Yuan Yu Y Danishefsky Samuel J SJ

Journal of the American Chemical Society 20090401 15

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 ...[more]

PMID: 19334679

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