Affiliation:
1. 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
2. Chemical Biology Research Center School of Pharmaceutical Sciences Chongqing University Chongqing 401331 P. R. China
3. Beijing National Laboratory for Molecular Sciences Beijing 100190 P. R. China
Abstract
AbstractCovalent crosslinking probes have arisen as efficient toolkits to capture and elucidate biomolecular interaction networks. Exploiting the potential of crosslinking in DNA‐encoded chemical library (DEL) selection methods significantly boosted bioactive ligand discovery in complex physiological contexts. Herein, we incorporated o‐nitrobenzyl alcohol (o‐NBA) as a photo‐activated lysine‐selective crosslinker into divergent DEL formats and achieved covalent capture of ligand‐target interactions featuring improved crosslinking efficiency and site‐specificity. In addition, covalent DEL selection was realized with the modularly designed o‐NBA‐functionalized mock libraries.
Funder
National Natural Science Foundation of China
Fundamental Research Funds for the Central Universities
Beijing National Laboratory for Molecular Sciences
Natural Science Foundation of Chongqing Municipality
High-end Foreign Experts Recruitment Plan of China
Subject
General Chemistry,Biochemistry,Organic Chemistry