Reversible Covalent Headpiece Enables Interconversion between Double- and Single-Stranded DNA-Encoded Chemical Libraries
Guixian Zhao
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
These authors contribute equally to this work.
Search for more papers by this authorShuting Zhong
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
These authors contribute equally to this work.
Search for more papers by this authorDr. Gong Zhang
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorDr. Yangfeng Li
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Dr. Yizhou Li
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, 400044 Chongqing, P. R. China
Search for more papers by this authorGuixian Zhao
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
These authors contribute equally to this work.
Search for more papers by this authorShuting Zhong
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
These authors contribute equally to this work.
Search for more papers by this authorDr. Gong Zhang
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorDr. Yangfeng Li
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Dr. Yizhou Li
Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Chemical Biology Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331 P. R. China
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, 400044 Chongqing, P. R. China
Search for more papers by this authorAbstract
The use of a proper encoding methodology is one of the most important aspects when practicing DEL technology. A “headpiece”-based double-stranded DEL encoding method is currently the most widely used for productive DEL. However, the robustness of double-stranded DEL construction conflicts with the versatility presented by single-stranded DEL applications. We here report a novel encoding method, which is based on a “reversible covalent headpiece (RCHP)”. The RCHP allows reversible interconversion between double- and single-stranded DNA formats, providing an avenue to robust synthesis and allowing for the applications in distinct setups. We have validated the versatility of this encoding method with encoded self-assembled chemical library and DNA-encoded dynamic library technology. Notably, based on the RCHP-settled library construction, a unique “ternary covalent complex” mediating ligand isolation methodology against non-immobilized targets was developed.
Open Research
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