Currently, click chemistry enabling rapid access to modular synthesis and bioconjugation, has become one of the most robust molecular assembly strategies in synthetic chemistry, modern drug discovery, biological research, nanotechnology, and materials science 2, 3, 4, 5, 6, 7, 8, 9, providing remarkable alternatives to conventional chemistry 10, 11, 12, 13, 14. Inspired by nature’s utilization of simple and powerful connecting reactions, the concept of click chemistry was first introduced by Kolb, Finn, and Sharpless as a synthetic strategy in 2001 (ref. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science. 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. 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. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. 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.
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