Use of Model Peptide Reactions for the Characterization of Kinetically Controlled Ligation

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• 作者：Joongoo Lee ; Yoonjin Kwon ; Brad L. Pentelute ; Duhee Bang
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：August 17, 2011
• 年：2011
• 卷：22
• 期：8
• 页码：1645-1649
• 全文大小：762K
• 年卷期：v.22,no.8(August 17, 2011)
• ISSN：1520-4812

文摘

Since the introduction of kinetically controlled ligation (KCL), a chemoselective reaction between a peptide-^伪thioarylester and a Cys-peptide-^伪thioalkylester, KCL has been utilized for the total chemical synthesis of large proteins (i.e., lysozyme and HIV-protease) by providing fully convergent synthetic routes. Although KCL has the potential to become an important chemistry for protein synthesis, the principle of KCL is not fully characterized. In particular, prior work on KCL has focused on the reactivity difference of the two different -^伪thioester forms鈥攁lkyl vs aryl. Another equally important feature of KCL, Xaa鈥揅ys ligation sites, has not been investigated. The work reported here describes combinatorial KCL reactions using model peptides to dissect the interplay of the Xaa₁, Xaa₂, -^伪thioarylester, and -^伪thioalkylester. Results from these studies provide fundamental insights into the KCL reaction, and will lead to the optimal synthetic route for the routine chemical synthesis of large target protein molecules.