Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA.
J Am Chem Soc. 2009 Apr 22;131(15):5432-7. doi: 10.1021/ja808705v.
Described herein is the chemical synthesis of the Cys(29)-Gly(77) glycopeptide domain (22) of erythropoietin. Our initial ligation strategy targeted a C --> N termini condensation between glycopeptide 3 and peptide 4. However, the reaction was hindered by the "unattainable" reactivity, mismatched polarity, and severe aggregation of the (glyco)peptide substrates. In contrast, by tuning the C-terminal acyl donor and using smaller peptide fragments, the Cys(29)-Gly(77) glycopeptide domain of erythropoietin was prepared through unconventional N --> C termini condensation reactions. The use of a p-cyanonitrophenyl ester and the development of a masked thiophenyl ester as acyl donors enabled us to promptly access glycopeptides bearing complex carbohydrates and offer potential synthetic applications beyond our current work.
本文描述了促红细胞生成素 Cys(29)-Gly(77)糖肽结构域（22）的化学合成。我们最初的连接策略是针对糖肽 3 和肽 4 之间的 C-N 端缩合。然而，由于（糖）肽底物的“不可及”反应性、不匹配的极性和严重的聚集，反应受到了阻碍。相比之下，通过调整 C 末端酰基供体并使用较小的肽片段，通过非传统的 N-C 端缩合反应制备了促红细胞生成素的 Cys(29)-Gly(77)糖肽结构域。使用对氰基硝基苯酯和开发掩蔽的噻吩酯作为酰基供体，使我们能够快速获得带有复杂碳水化合物的糖肽，并为超出我们当前工作的潜在合成应用提供了可能性。
