文献类型：期刊文献

中文题名：Mechanism of Imidazole-Promoted Ligation of Peptide Phenyl Esters

英文题名：Mechanism of Imidazole-Promoted Ligation of Peptide Phenyl Esters

作者：Wang Chen[2];Liu Lei[1]

机构：[1]Tsinghua Univ, Dept Chem, Beijing 10084, Peoples R China;[2]Shaoxing Univ, Coll Chem & Chem Engn, Shaoxing 312000, Zhejiang, Peoples R China

年份：2012

卷号：30

期号：9

起止页码：1974

中文期刊名：中国化学：英文版

外文期刊名：CHINESE JOURNAL OF CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:000309400700011)、、Scopus(收录号：2-s2.0-84867020989)、CSCD2011_2012、WOS、CSCD

基金：This study was supported by the national "973" grants from the Ministry of Science and Technology (No. 2011CB965300) and NSFC (No. 20932006, 91013007).

语种：英文

中文关键词：合成肽;结扎;咪唑;苯酯;机制;蛋白质化学;C-末端;空间位阻

外文关键词：mechanism; native chemical ligation; phenyl ester; thioester; imidazole

外文摘要：Imidazole-promoted ligation of peptide phenyl esters was recently found to be a complementary method for protein chemical synthesis. Theoretical calculations have been carried out to understand the detailed mechanism of this particular ligation process. It is found that both the reaction of the phenyl ester with imidazole and the reaction of the acyl imidazole intermediate with cysteine proceed through an addition-elimination mechanism. The cleavage of the C?O bond in the reaction between the phenyl ester and imidazole is the rate-limiting step of the overall ligation process. Interestingly, although the imidazole-promoted phenyl ester ligation has a higher free energy barrier than the conventional thiophenol-promoted native chemical ligation for a sterically less hindered C-terminal amino acid (e.g. gylcine), for a sterically hindered C-terminal amino acid (e.g. proline) the imidazole-promoted phenyl ester ligation is calculated to be more favorable than the conventional thiophenol-promoted native chemical ligation.