1. Psoralen as an interstrand DNA crosslinker in the selection of DNA-Encoded dynamic chemical library
- Author
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Jianzhao Peng, Xiaoyu Li, Yu Zhou, and Wenyin Shen
- Subjects
0301 basic medicine ,High-throughput screening ,Biophysics ,Computational biology ,Biochemistry ,Chemical library ,Small Molecule Libraries ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Discovery ,Dynamic combinatorial chemistry ,Combinatorial Chemistry Techniques ,Molecular Biology ,Psoralen ,DNA-encoded chemical library ,Drug discovery ,Ficusin ,Cell Biology ,DNA ,Ligand (biochemistry) ,Photochemical Processes ,030104 developmental biology ,Cross-Linking Reagents ,chemistry ,030220 oncology & carcinogenesis - Abstract
DNA-encoded chemical library (DEL) has emerged as a powerful technology for ligand discovery in biomedical research. Recently, we have developed a DNA-encoded dynamic library (DEDL) approach by incorporating the concept of dynamic combinatorial library (DCL) with DELs. DEDL has shown excellent potential in ligand discovery towards a variety of protein targets. However, the requirement of having a pair of unnatural p-stilbazoles as the interstrand DNA crosslinker has limited the chemical diversity of DEDLs. Here, we replaced p-stilbazole with psoralen (PS) and tested the feasibility of psoralen as the crosslinker in DEDL selection. Since psoralen is commercially available and does not require any special crosslinking partner, existing DELs may be directly used to create high-diversity DEDLs. This study is expected to greatly facilitate the development of DEDLs as a versatile tool in drug discovery.
- Published
- 2020