Generation of an S-peptide via an N-S acyl shift reaction in a TFA solution
Generation of an S-peptide via an N-S acyl shift reaction in a TFA solution
复制标题
DOI：
10.1246/bcsj.79.1773
复制
发表时间：
2006-11-15
影响因子：
4
通讯作者：
Aimoto, Saburo
中科院分区：
文献类型：
--
作者：
Nakamura, Ken'ichiroh;Sumida, Megumi;Aimoto, Saburo
采用核磁共振（NMR）、反相高效液相色谱（RP）和质谱（MS）分析，证实了巯基多肽在三氟乙酸（TFA）溶液中发生了N-S酰基移位反应。含有半胱氨酸残基的模型肽在TFA溶液中转化为s肽。在RP-HPLC分析中，即使使用含有0.1% TFA的洗脱液，s肽也能快速转化为原始肽。具有n -2-巯基-4,5-二甲氧基苯基（Dmmb）基团的肽也通过TFA处理转化为s肽，与Dmmb基团的硫醇形成硫酯键。将反应混合物直接注入反相高效液相色谱分离得到s肽，并与2-巯基乙磺酸钠通过分子间硫醇交换反应转化为相应的2-硫乙基硫酯。2-磺乙基肽硫酯被广泛用于多肽合成。在有或没有辅助基团的肽中观察到的N-S酰基移位反应为肽硫酯的制备提供了新的途径。
An N-S acyl shift reaction of thiol-containing peptides in a trifluoroacetic acid (TFA) solution was confirmed by a combination of C-13 NMR spectroscopy, reversed-phase (RP) HPLC, and MS analyses. A model peptide containing a cysteine residue was transformed into an S-peptide in a TFA solution. The S-peptide was quickly transformed to the original peptide during RP-HPLC analysis even when an eluent that contained 0.1% TFA was used. A peptide that had an N-2-mercapto-4,5-dimethoxybenzyl (Dmmb) group was also transformed into an S-peptide, forming a thioester bond with the thiol of the Dmmb group by TFA treatment. The generated S-peptide was isolated by directly injecting the reaction mixture into a RP-HPLC and was readily converted to the corresponding 2-sulfoethyl thioester via an intermolecular thiol exchange reaction with sodium 2-mercaptoethanesulfonate. The 2-sulfoethyl peptide thioester is widely used as a building block in polypeptide synthesis. The N-S acyl shift reaction observed in peptides with or without an auxiliary group provides a new route for the preparation of peptide thioesters.