Scholarlink

<p>Native chemical ligation (NCL) has emerged as the most extensively employed chemoselective reaction in chemical protein synthesis (CPS). Nevertheless, the inherently low reactivity of peptide alkyl thioesters often necessitates the use of excessive nucleophilic additives in NCL to facilitate the reaction. Herein, we describe a rapid, and additive-free peptide ligation reaction between peptide thioacid and <i>N</i>-terminal cysteinyl peptide without epimerization in the present vinyl thianthrenium tetrafluoroborate (VTT). VTT promotes quantitative and chemoselective activation of fully unprotected <i>C</i>-terminal peptide thioacids into thioester intermediates, which demonstrate exceptional reactivity, facilitating rapid NCL in an additive-free manner with high yields. This additive-free strategy is fully compatible with post-ligation desulfurization, allowing for a streamlined one-pot process that enhances the overall efficiency and simplicity of CPS workflows. The effectiveness of this methodology is demonstrated by synthesizing hyalomin-3 from two fragments through a one-pot thioesterification-ligation-desulfurization protocol and ubiquitin through a one-pot <i>C-to-N</i> sequential three-segment condensation (six steps in one pot).</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Rapid vinyl thianthrenium tetrafluoroborate-promoted thioacid-based native chemical ligation and its applications in chemical protein synthesis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月2日

查看全文
  • Hanghang Li,
  • Shujuan Xu,
  • Zhichao Zhang,
  • Rujie Xie,
  • Jingying Liu,
  • Junjie Ma,
  • Congshen Zheng,
  • Changmai Chen,
  • Wei Chen,
  • Jiaan Liu

摘要

Native chemical ligation (NCL) has emerged as the most extensively employed chemoselective reaction in chemical protein synthesis (CPS). Nevertheless, the inherently low reactivity of peptide alkyl thioesters often necessitates the use of excessive nucleophilic additives in NCL to facilitate the reaction. Herein, we describe a rapid, and additive-free peptide ligation reaction between peptide thioacid and N-terminal cysteinyl peptide without epimerization in the present vinyl thianthrenium tetrafluoroborate (VTT). VTT promotes quantitative and chemoselective activation of fully unprotected C-terminal peptide thioacids into thioester intermediates, which demonstrate exceptional reactivity, facilitating rapid NCL in an additive-free manner with high yields. This additive-free strategy is fully compatible with post-ligation desulfurization, allowing for a streamlined one-pot process that enhances the overall efficiency and simplicity of CPS workflows. The effectiveness of this methodology is demonstrated by synthesizing hyalomin-3 from two fragments through a one-pot thioesterification-ligation-desulfurization protocol and ubiquitin through a one-pot C-to-N sequential three-segment condensation (six steps in one pot).