A Comparison of Boc and Fmoc SPPS Strategies for the Preparation of C-Terminal Peptide α-Thiolesters: NY-ESO-1 39Cys-68Ala-COSR
A Comparison of Boc and Fmoc SPPS Strategies for the Preparation of C-Terminal Peptide α-Thiolesters: NY-ESO-1 39Cys-68Ala-COSR
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DOI：
10.1002/bip.22223
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发表时间：
2013-07-01
期刊：
影响因子：
2.9
通讯作者：
Brimble, Margaret A.
中科院分区：
文献类型：
--
作者：
Harris, Paul W. R.;Brimble, Margaret A.
描述了源自癌睾丸抗原NY-ESO-1的带有C末端α-硫醇酯的多肽的合成。采用叔丁氧羰基固相肽合成，使用巯基丙酸连接基将硫醇酯部分安装在树脂上，从而不需要合成后操作，并且在用HF从树脂裂解后递送必需的α-硫醇酯多肽。同时检查了几种9-芴基甲氧基羰基固相肽合成方法，其中需要以合成后的方式引入硫醇酯。这些包括在两个不同的“安全锁”接头上的合成，即N-烷基-N-酰基磺酰胺和N-酰基苯并咪唑酮，其中硫醇酯由活化的前体产生。还研究了直接硫醇酯化反应中硫醇与C-末端羧酸酯的缩合。当使用三种基于9-芴基甲氧基羰基的方法中的任何一种时，线性多肽可以直接组装在固相树脂上；然而，C 端羧基的硫醇酯化（完全侧链保护的肽）被证明是安装 C 端硫醇酯的最有效的后组装方法。 (C) 2013 年 Wiley 期刊公司。
The synthesis of a polypeptide derived from the cancer testis antigen NY-ESO-1 bearing a C-terminal a-thiolester is described. Employing tert-butyloxycarbonyl solid phase peptide synthesis the thiolester moiety was installed on-resin using a mercaptopropionic acid linker, thereby requiring no post synthetic manipulations and delivering the requisite alpha-thiolester polypeptide after cleavage from the resin with HF. Several 9-fluorenylmethyloxycarbonyl solid phase peptide synthesis approaches whereby the thiolester was required to be introduced in a post synthesis manner were examined concurrently. These comprised syntheses on two different "safety catch" linkers, an N-alkyl-N-acyl sulphonamide and an N-acyl benzimidazolone wherein the thiolester is generated from an activated precursor. The condensation of a mercaptan with the C-terminal carboxylate in a direct thiolesterification reaction was also examined. When using either of the three 9-fluorenylmethyloxycarbonyl-based approaches, the linear polypeptide could be assembled straightforwardly on the solid phase resin; however, a thiolesterification of the C-terminal carboxyl the fully side chain protected peptide proved to be the most effective post-assembly method for the installation of the C-terminal thiolester. (C) 2013 Wiley Periodicals, Inc.