On March 19, 2018, the research team led by Researcher Li Yizhou of the School of Pharmaceutical Sciences, CQU, published a research paper titled “Versatile Protein Recognition by the Encoded Display of Multiple Chemical Elements on a Constant Macrocyclic Scaffold” on Springer Nature, a sub-journal of Nature (factor of influence of 2017: 25.87), in collaboration with the team led by Professor Dario Neri of the Institute of Pharmacology of Swiss Federal Institute of Technology Zurich (ETH). Researcher Li Yizhou is the first author and one of the corresponding co-authors of the paper. The other two corresponding co-authors are Dr. Jörg Scheuermann and Professor Dario Neri. This is the first paper that has been published on the journal with Chongqing University as the first corresponding author.
DNA-Encoded Chemical Libraries is an emerging drug R&D means. This technique combines chemical synthesis with ENA encoding strategy in an organic manner to efficiently build a super-large-scale molecular library (with 1,012 compounds and carry out High-Throughput Screening of disease related targets. With this technique, it is able to carry out High-Throughput Screening with low cost and high efficiency, which was previously only possible in large pharmaceuticals companies. In recent years, this technique named “scanning barcode and finding new drugs” has seen rapid development, and has been used by a number of multinational pharmaceuticals companies to develop new drugs, with a series clinical compounds obtained.
This paper contains the combining technique of DNA-encoded chemical libraries based on Constant Macrocyclic Scaffold, which was used to obtain a molecular library that contains 35,393,112 macrocyclic compounds. DNA-encoded macrocyclic molecular library was screened based on 9 different target proteins to obtain macrocyclic compounds with specific binding. The research findings indicate that even with tumor necrosis factor, a small molecule for which “drugs are hard to develop”, as the target, active compound related to different protein targets can still be obtained from the same DNA-encoded library through reasonable design of macrocyclic scaffold.
The research work is funded by the starting funding of ETH, Swiss National Science Foundation (SNSF) and European Research Council (ERC), and the “Hundred Talents Program” of Chongqing University.
Link of the paper: https://www.nature.com/articles/s41557-018-0017-8