Byrne Stephen A, Bedding Max J, Corcilius Leo, Ford Daniel J, Zhong Yichen, Franck Charlotte, Larance Mark, Mackay Joel P, Payne Richard J
School of Chemistry, The University of Sydney Sydney NSW 2006 Australia
Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney Sydney NSW 2006 Australia.
Chem Sci. 2021 Sep 30;12(42):14159-14166. doi: 10.1039/d1sc03127a. eCollection 2021 Nov 3.
The modification of peptides and proteins has emerged as a powerful means to efficiently prepare high value bioconjugates for a range of applications in chemical biology and for the development of next-generation therapeutics. Herein, we report a novel method for the chemoselective late-stage modification of peptides and proteins at cysteine in aqueous buffer with suitably functionalised diaryliodonium salts, furnishing stable thioether-linked synthetic conjugates. The power of this new platform is showcased through the late-stage modification of the affibody zEGFR and the histone protein H2A.
肽和蛋白质的修饰已成为一种有效的手段，可高效制备高价值生物共轭物，用于化学生物学的一系列应用以及下一代治疗药物的开发。在此，我们报告了一种在水性缓冲液中使用适当功能化的二芳基碘鎓盐对肽和蛋白质中的半胱氨酸进行化学选择性后期修饰的新方法，从而提供稳定的硫醚连接的合成共轭物。通过亲合体zEGFR和组蛋白H2A的后期修饰展示了这个新平台的强大功能。
