Chinese Academy of Sciences Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China.
Nat Commun. 2020 Oct 29;11(1):5472. doi: 10.1038/s41467-020-19274-y.
The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.
点击化学的出现对许多领域产生了深远的影响，并推动了对可靠反应的需求，以扩展点击化学工具箱。然而，开发新的系统来满足点击化学的标准仍然是非常可取的，但具有挑战性。在这里，我们报告了光诱导伯胺和邻硝基苄醇环化（PANAC）作为一种光点击反应的发展，通过伯胺作为直接点击处理，实现了各种小分子和天然生物分子的快速和模块化功能化。PANAC 光点击反应具有时间控制、良好的生物相容性、可靠的化学选择性、优异的效率、易于获得的反应物、操作简单和温和条件等内在优势，可用于直接多样化药物和生物相关分子、未保护肽和天然蛋白质的赖氨酸特异性修饰、内源性激酶的时间分析以及活细胞中的细胞器靶向标记。该策略为有机合成、生物偶联、药物化学、化学生物学和材料科学提供了一个通用的平台。
