Nakamura Ken'ichiroh, Kanao Tomoki, Uesugi Tomoya, Hara Toshiaki, Sato Takeshi, Kawakami Toru, Aimoto Saburo
Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.
J Pept Sci. 2009 Nov;15(11):731-7. doi: 10.1002/psc.1164.
An efficient method of peptide thioester synthesis is described. The reaction is based on an N-4,5-dimethoxy-2-mercaptobenzyl (Dmmb) auxiliary-assisted N-S acyl shift reaction after assembling a peptide chain by Fmoc-solid phase peptide synthesis. The Dmmb-assisted N-S acyl shift reaction proceeded efficiently under mildly acidic conditions, and the peptide thioester was obtained by treating the resulting S-peptide with sodium 2-mercaptoethanesulfonate. No detectable epimerization of the amino acid residue adjacent to the thioester moiety in the case of Leu was found. The reactions were also amenable to the on-resin preparation of peptide thioesters. The utility was demonstrated by the synthesis of a 41-mer peptide thioester, a phosphorylated peptide thioester and a 33-mer peptide thioester containing a trimethylated lysine residue.
本文描述了一种高效的肽硫酯合成方法。该反应基于在通过Fmoc-固相肽合成组装肽链后，由N-4,5-二甲氧基-2-巯基苄基（Dmmb）辅助的N-S酰基转移反应。Dmmb辅助的N-S酰基转移反应在温和酸性条件下高效进行，通过用2-巯基乙磺酸钠处理所得的S-肽来获得肽硫酯。在亮氨酸的情况下，未发现硫酯部分相邻氨基酸残基有可检测到的差向异构化。这些反应也适用于肽硫酯的树脂上制备。通过合成一个41肽硫酯、一个磷酸化肽硫酯和一个含有三甲基化赖氨酸残基的33肽硫酯证明了其效用。
