Install control switches for every protein in living cells

It is of great scientific significance to carry out in situ studies of protein functions in living cells and other physiological environments. Recently, the reporter learned from Peking University that Chen Peng's team of Peking University College of Chemical and Molecular Engineering and Wang Chu's team have developed a new technology for instantaneous activation of proteins in living cells or animals. The related results are published online in the Journal Nature.

Chen Peng's research group has been devoted to the development of in situ activation technology of proteins for a long time, hoping to install "regulatory switches" for every protein in living cells. Previously, they proposed a "chemical decommissioning" strategy, which could regulate the activity of key protein residues through chemical protection and decommissioning reactions. Due to the variety of intracellular proteins and the different mechanisms of activity regulation, this method is still limited by the kinds of amino acids that can be released from the cage, and can not be applied to all proteins. In order to solve this bottleneck problem, Chen Peng's group and Wang Chu's group put forward a new strategy of "adjacent decommissioning". By introducing an unnatural tyrosine (ONBY) with a photoprotective group near the active center of protein, the activity of ONBY can be remotely disturbed and inhibited, and then the protective group can be removed and its activity can be restored by the photodetachment reaction. In this process, they combined the unclassified technology of inheritable coded non-natural amino acids with computer aided design screening technology to achieve high time-resolved in situ activation of a series of different proteins, providing a universal technology for studying the dynamic regulation mechanism of proteins in living cells and animals. Using this new method, researchers established and validated a series of original applications, such as "kinase orthogonal activation and signal transduction regulation", "time-resolved proteomics analysis", "toxin protein-based antineoplastic protein prodrug". Zhang Lihe, academician of the Chinese Academy of Sciences, pointed out that this work is an important progress in the field of chemical biology. It provides a key technology for studying the dynamic function of proteins in living cells and animals, and also opens up a new frontier for biological orthogonal reactions.