Native chemical ligation at valine
Native chemical ligation at valine
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DOI：
10.1002/anie.200801590
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Seitz, Oliver
中科院分区：
文献类型：
--
作者：
Haase, Christian;Rohde, Heike;Seitz, Oliver
在肽段偶联的技术中，天然化学连接是最有用的技术之一自发现以来，它已成为化学合成蛋白质的有力工具，包括标记或翻译后修饰的蛋白质和含有非蛋白质原性氨基酸的蛋白质在天然化学连接中，无保护的c端肽硫酯与无保护的n端半胱氨酸残基发生反应。对稀有氨基酸半胱氨酸的需求限制了其在天然蛋白质合成中的适用性。已经开发了几种方法来允许进入其他更常见的结扎部位。在扩展的天然化学连接中，半胱氨酸结构通过附着在肽片段末端的可移动辅助基团来模拟通常，在辅助结构中包含富电子芳香环体系，以促进结扎后的酸解去除。[5e-k]甘氨酸-甘氨酸肽键的形成通常没有问题。然而，仲胺的反应性随着连接部位空间需求的增加而迅速降低。因此，在大块氨基酸如缬氨酸或异亮氨酸的结扎尚未实现。最近，糖辅助结扎已被报道，这是特别感兴趣的糖肽合成
Among the techniques employed for coupling peptide segments,[1] native chemical ligation is among the most useful.[2] Since its discovery it has become a powerful tool for the chemical synthesis of proteins including labeled or posttranslationally modified proteins and proteins that contain nonproteinogenic amino acids.[3] In the native chemical ligation an unprotected C-terminal peptide thioester reacts with an unprotected N-terminal cysteine residue. The requirement for the rare amino acid cysteine limits the applicability in the synthesis of naturally occurring proteins. Several approaches have been developed to allow access to other, more common ligation sites.[4]In the extended native chemical ligation the cysteine structure is mimicked by means of a removable auxiliary group that is attached to the Nterminus of the peptide fragment.[5] Typically, electron-rich aromatic ring systems are included in the auxiliary structure to facilitate acidolytic removal subsequent to the ligation.[5e–k] The formation of glycine–glycine peptide bonds usually proceeds without problems. However, the reactivity of the secondary amine rapidly decreases with increasing steric demand at the ligation site. Thus, ligation at bulky amino acids such as valine or isoleucine has not been achieved. Recently, sugar-assisted ligation has been reported, which is of particular interest for glycopeptide synthesis.[6]