Department of Chemistry, Iowa State University, Ames, Iowa 50011, United States.
J Am Chem Soc. 2022 Dec 14;144(49):22397-22402. doi: 10.1021/jacs.2c09085. Epub 2022 Dec 5.
Amidines are a structural surrogate for peptide bonds, yet have received considerably little attention in peptides due to limitations in existing methods to access them. The synthetic strategy developed in this study represents the first robust and general procedure for the introduction of amidines into the peptide backbone. We exploit and further develop the utility and efficiency of thioimidate protecting groups as a means to side-step reactivity that ultimately renders existing methods unsuitable for the installation of amidines along the main-chain of peptides. This work is significant because it describes a generally applicable path to access unexplored peptide designs and architectures for new therapeutics made possible by the unique properties of amidines.
脒基是肽键的结构替代物，但由于现有方法在获取脒基方面存在限制，因此在肽中受到的关注甚少。本研究中开发的合成策略代表了在肽主链中引入脒基的第一个稳健且通用的程序。我们利用并进一步发展硫代亚氨基保护基的实用性和效率，作为回避反应性的一种手段，而这种反应性最终使现有方法不适合在肽的主链中安装脒基。这项工作意义重大，因为它描述了一种普遍适用的方法，可以获得通过脒基的独特性质成为可能的新治疗方法的未探索的肽设计和结构。
