Install a regulatory switch for every protein in a living cell

important scientific significance to carry out in-place research on protein function in physiological environments such as living cells. Recently, the reporter learned from Peking University, Peking University School of Chemistry and Molecular Engineering Chen Peng group and Wangchu team developed a living cells or animals instantaneous activation of protein universal new technology, the results published online in the journal Nature.Chen Peng's team has long been committed to the development of in-place protein activation technology, hoping to install a "regulatory switch" for every protein in living cells. Previously, they proposed a "chemical de-cage" strategy, through the chemical protection of protein-critical residues and de-protection reaction, to achieve its activity "off-on" regulation. Due to the wide variety of proteins in cells and the different mechanisms of activity regulation, the method is still limited by the types of amino acids available for de-cage, and cannot be applied to all proteins.in order to solve this bottleneck problem, Chen Peng task force and Wangchu task force put forward a new strategy of "proximity out of the cage". Remote interference and inhibition of the activity of a non-natural tyrosine (ONBY) with a photoprotein protection group can be achieved by introducing a non-natural tyrosine with a photoprotege group near the protein activity center, and its activity can then be restored by removing the protective group through a "light removal" reaction. In this process, they combined the non-natural amino acid de-cageing technique with computer-aided design screening technology to achieve high time-resolution in-place activation on a series of different kinds of proteins, providing a universal technique for studying the dynamic regulatory mechanism of proteins in living cells and living animals.Using this new method, the researchers built and validated a series of original applications such as kinase orthotic activation and signal transductive regulation, time-distinguished proteomic analysis, and anti-tumor protein pre-drugs based on toxin proteins.Zhang Li, a member of the Chinese Academy of Sciences, pointed out that the work is an important advance in the field of chemical biology, providing key techniques for the study of protein dynamic function in living cells and living animals, and opening up new frontiers for bio ortho reactions. (Science and Technology Daily)