An o-nitrobenzyl scaffold for peptide ligation:: synthesis and applications
An o-nitrobenzyl scaffold for peptide ligation:: synthesis and applications
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DOI：
10.1016/j.bmc.2004.02.039
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发表时间：
2004-05-15
影响因子：
3.5
通讯作者：
Dawson, PE
中科院分区：
文献类型：
--
作者：
Marinzi, C;Offer, J;Dawson, PE
化学连接方法有助于无保护多肽在水溶液中的化学选择性组装。在这里，描述了两种光敏助剂，它们将天然化学连接的适用性扩大到非半胱氨酸靶标。这些辅助剂旨在允许与硫代酯肽反应，在两个初始片段之间产生一个酰胺键。在温和的光解条件下，在连接结合处形成的邻硝基苄基叔基苯甲酰胺可以转化为天然的酰胺基团。藜芦基辅助在多肽的纯化和连接过程中被发现过于不稳定。然而，基于邻硝基苄基的助剂显示出在常规多肽和蛋白质合成中的一般应用的所有必要性质。此外，N-末端连接的辅助剂可以有效地光解，这为光笼化胺的合成提供了一种新的方法。介绍了多肽链的固相引入、连接性质和在水中的光解，并对该方法与潜在的脆性多肽侧链的相容性进行了仔细的研究。(C)2004爱思唯尔有限公司。保留所有权利。
Chemical ligation approaches facilitate the chemoselective assembly of unprotected peptides in aqueous solution. Here, two photolabile auxiliaries are described that enlarge the applicability of native chemical ligation to non-cysteine targets. The auxiliaries, designed to allow reaction with thioester peptides, generate an amide bond between the two initial fragments. The o-nitrobenzyl tertiary benzylamide that is formed at the ligation junction can be transformed into a native amide group under mild photolysis conditions.The veratryl auxiliary was found to be excessively labile during peptide purification and ligation. However, the auxiliary based on the o-nitrobenzyl group shows all the necessary properties for a general application in routine peptide and protein synthesis. In addition, the auxiliary linked to the N-terminus can be efficiently photolyzed, suggesting a new approach for the generation of photocaged amines.Synthesis. solid phase introduction onto peptide chains, ligation properties and photolysis in water are described, and a careful study of compatibility of the method with potentially fragile peptide side chains is reported. (C) 2004 Elsevier Ltd. All rights reserved.