Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.
Angew Chem Int Ed Engl. 2024 Jul 29;63(31):e202402880. doi: 10.1002/anie.202402880. Epub 2024 Jun 26.
Lysine-specific peptide and protein modification strategies are widely used to study charge-related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge-related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge-related protein properties, such as liquid-liquid phase separation behaviour of α-synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine-containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins.
赖氨酸特异性肽和蛋白质修饰策略被广泛用于研究与电荷相关的功能和应用。然而，这些策略通常会导致赖氨酸上正电荷的损失，从而显著影响蛋白质的电荷相关性质。在此，我们报告了一种策略，即在水相条件下使用腈和羟胺将赖氨酸侧链上的胺选择性转化为脒基，同时保留正电荷。各种未保护的肽和蛋白质都可以高转化率进行修饰。此外，反应性的脒基部分和衍生的修饰位点能够实现后续的二次修饰。值得注意的是，修饰过程中保留了正电荷。因此，与正电荷相关的蛋白质性质，如α-突触核蛋白的液-液相分离行为，不受影响。该策略随后被应用于富含赖氨酸的蛋白质，开发了一种具有出色机械性能的含脒共凝聚体 DNA 复合物。总体而言，我们的创新策略为探索带正电荷蛋白质的特性提供了新途径。
