Light-induced Indazolone Synthesis Reaction And Its Application In Protein Labeling

We mainly developed a light-induced indazolone synthesis reaction and its application in protein labeling,with the application of light-induced lysine selective labeling technology in protein modification,and a new method of light-induced synthesis of indazolone heterocycles.The chemical modification of proteins has become a very important research field.Highefficiency protein chemical modification methods have been widely used in many fields,such as the development of new protein macromolecular drugs and the structure and function research of specific proteins.Light-induced protein chemoselective labeling can realize the time and spacecontrol of biomolecules by adjusting the parameters of the light source.Lysine residue is the most abundant amino acid in the proteome,and there has been no reports of light-induced protein selective labeling based on lysine residue.We used the photochemical reaction of o-nitrobenzyl alcohol derivative and lysine residue as a model to screen and optimize conditions,and developed a new method of light-induced indazolone formation of lysine residue-selective protein labeling.The method has simple operation,mild conditions,can realize selective labeling of lysine residue in vitro and in vivo,has an excellent reaction efficiency and time controllability.This new method proves the feasibility of direct modification and rapid functionalization of natural proteins,and is of great significance to the research of protein modification,protein biomacromolecule drugs,medicinal chemistry and chemical biology.Indazolone derivatives have received extensive attention because of their potentially important physiological activities.Many methods have been developed to construct indazolone heterocycles,but most of them use transition metal catalysis,which makes the reaction complicated or takes a long time.We have screened a series of photochemical reactions between o-nitrobenzylamine derivatives and primary amine,and developed a new method for rapid construction of indazolone heterocycles through photochemical cyclization reactions in a buffer system,successfully.This new method is of great significance not only in the synthesis of physiologically active drug molecules,but also in the development of a new generation of light-induced lysine residue selective labeling of proteins,the design of photoactive molecular probes and their application in molecular imaging.