A research paper titled “selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells” written by the chemicobiology team of the School of Pharmaceutical Sciences, Chongqing University, in collaboration with teams of University of Hong Kong and Second Military Medical University, was published in Nature Chemistry on December 21, 2020. Professor Li Yizhou of CQU, Professor Li Xiaoyu of University of Hong Kong and Professor Cao Yan of the Second Military Medical University are corresponding co-authors of the paper. This is the second time the chemicobiology team of the School of Pharmaceutical Sciences, Chongqing University has published representative research findings in the journal. (Click the following link for more information on the research https://www.nature.com/articles/s41557-018-0017-8.)
Cell membrane proteins are a very important class of disease-related targets. Membrane proteins are widely recognized as "drug resistant" targets in the area of medicine due to their diversity in types, unstable structure and complex cell membrane environment. It is of great scientific significance and practical value to develop new drug discovery methods for cell membrane proteins. Based on the achievements already made on the research of DNA-Encoded Chemical Libraries, the joint research team has developed a new drug discovery method for membrane proteins: through specific DNA probes, the team accurately traced membrane proteins in the complex physiological environment of living cells. Combined with the characteristics of low cost and high efficiency of DEL, the team was able to achieve high-throughput drug screening for membrane proteins on living cells. This study shows that active compounds can be obtained through this technology for the "drug resistant" targets such as G-protein coupled receptor (GPCR) super-family and epidermal growth factor receptor (EGFR).
Li Yizhou and Li Xiaoyu jointly proposed this new method of drug discovery, and led the research work. Nie Qigui and Yang Shilian, postgraduate students of the School of Pharmaceutical Sciences, Chongqing University, and Huang Cen, an undergraduate student (who is now at the University of Hong Kong to study for doctor's degree), participated in and completed part of the experimental work. The research work is supported by the National Natural Science Foundation of China, Chongqing Outstanding Youth Funds, Chongqing Oversea Students Entrepreneurship Program and the basic scientific research funds allocated by the central government to colleges and universities.
Specific DNA probes were used to label the surface proteins of live cells, so as to realize drug discovery based on DEL.