Toward Homogeneous Erythropoietin: Chemical Synthesis of the Ala1−Gly28 Glycopeptide Domain by “Alanine” Ligation
- 31 March 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 131 (15) , 5438-5443
- https://doi.org/10.1021/ja808707w
Abstract
The Ala1−Gly28 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 Ala19. 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 Cys29 without further functionalization.Keywords
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