Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation.
Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation.
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DOI:
10.1021/ja808707w
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发表时间:
2009-04-22
影响因子:
15
通讯作者:
Danishefsky SJ
中科院分区:
文献类型:
--
作者:
Kan C;Trzupek JD;Wu B;Wan Q;Chen G;Tan Z;Yuan Y;Danishefsky SJ
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.
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