Turning biological cells into reaction factories-the development and application of living cell chemical reaction tools in the second prize of the 2020 National Natural Science Award Project

As we all know, living organisms can be called a chemical factory

The team of Professor Chen Peng from Peking University gave a positive answer

Bio-orthogonal reaction refers to a type of chemical reaction that can be carried out in a biological system without interfering with natural biochemical processes

However, the conditions of the bio-orthogonal reaction are extremely harsh.

At the beginning of the research, the bioorthogonal reaction mainly refers to the coupling reaction, which is used to label, trace, enrich or modify the target biomolecule in the complex environment of the organism

With the deepening of research and the development of applications, Chen Peng's team has developed a bio-orthogonal shearing reaction based on chemical bond cleavage together with international counterparts

In 2014, the research group realized the in-situ activation of biological macromolecules represented by protein.

In 2018, Chen Peng’s team cooperated with the Gaoyuan Research Group of the National Nanoscience Center to coordinate the use of enzyme-triggered supramolecular self-assembly and bio-orthogonal bond breaking reactions to achieve in-situ and specific prodrug activation inside tumor cells, which not only reduces The toxic and side effects of anti-cancer drugs, and enhance the ability of targeting activation

　　They designed and synthesized short peptides with prodrug activation switch enzymes in response to assembly precursors, using the over-expressed phosphatase of cervical cancer cells to construct functional nano-assemblies in situ in the tumor, so that the prodrug activation switch can achieve tumor targeting and a large number of Enriched

　　In 2021, Chen Peng and Lin Jian's team at Peking University developed a universal membrane protein targeted degradation technology and obtained the membrane protein targeted degradation gene GlueTAC

　　Experimental results show that GlueTAC can rapidly mediate the endocytosis and degradation of target proteins in a variety of cancer cells, including lung cancer, breast cancer, and melanoma, so as to activate T cells more efficiently and lastingly.

　　The above two cases also show that the bio-orthogonal reaction has brought revolutionary technology to the study of life processes, and also provided pioneering methods for medical research, clinical diagnosis, and new drug development, becoming the core area of ​​chemical biology.

　　Regarding the current situation of bio-orthogonal reactions, Chen Peng said frankly that bio-orthogonal reactions are facing a critical stage of innovation expansion and application upgrade.

　　However, it is foreseeable that in accordance with the development trend of extensional upgrades, the demand for bio-orthogonal reactions of living animals and even higher animals will become more and more urgent