朝着同型促红细胞生成素迈进：通过“丙氨酸”连接化学合成 Ala1-Gly28 糖肽结构域。
Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation.
机构信息
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
出版信息
J Am Chem Soc. 2009 Apr 22;131(15):5438-43. doi: 10.1021/ja808707w.
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.
摘要
EPO 的 Ala(1)-Gly(28)糖肽片段（28）通过化学合成制备为单一糖型。合成中的关键步骤包括通过 Lansbury 天冬氨酸酰化将复杂的十二聚糖（7）连接到七肽上，通过天然化学连接将肽 19 与糖肽结构域 18 连接，以及在连接点选择性脱硫以揭示天然 Ala(19)。该糖肽片段（28）既含有必需的 N-连接十二聚糖，又含有 C 末端（α）硫酯柄，后者的特征是可以直接与带有 N 末端 Cys(29)的糖肽片段偶联，而无需进一步功能化。
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