A new scaffold for amide ligation
A new scaffold for amide ligation
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DOI：
10.1016/s0968-0896(01)00136-5
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发表时间：
2001-09-01
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;Bark, SJ;Dawson, PE
高度化学选择性的酰胺形成连接反应促进了蛋白质和其他酰胺连接的生物缀合物的合成。为了推广这种方法，开发了 N-α-2-苯基乙硫醇支架，以类似于与 N 末端半胱氨酸残基的天然化学连接的方式促进 S 到 N 酰基转移。对水溶液中支架介导的连接反应的分析表明，Xaa-Gly 连接处的连接速率足以合成大多肽。此外，还发现连接速率与支架中的立体中心无关，并且S-至AT-酰基转移是速率限制的。这些研究表明，N-α-2-苯基乙硫醇支架是开发用于形成 Xaa-Gly 肽和其他无阻碍酰胺的连接化学的良好候选者。 (C) 2001 Elsevier Science Ltd. 保留所有权利。
Highly chemoselective amide forming ligation reactions have facilitated the synthetic access to proteins and other amide-linked bioconjugates. In order to generalize this approach, a N-alpha-2-phenyl ethanethiol scaffold has been developed to promote S to N acyl transfer in a manner analogous to native chemical ligation with N-terminal cysteine residues. Analysis of scaffold-mediated ligation reactions in aqueous solution indicate that the ligation rate at Xaa-Gly junctions is sufficient for the synthesis of large polypeptides. In addition, it was found that the ligation rate is independent of the stereocenter in the scaffold and S- to AT-acyl transfer is rate limiting. These studies indicate that the N-alpha-2-phenyl ethanethiol scaffold is a good candidate for the development of a ligation chemistry for the formation of Xaa-Gly peptides and other unhindered amides. (C) 2001 Elsevier Science Ltd. All rights reserved.