Covalent Capture and Selection of DNA‐Encoded Chemical Libraries via Photo‐Activated Lysine‐Selective Crosslinkers
Haimei Wei, Tianyang Zhang, Yangfeng Li, Yangfeng Li, Gong Zhang, Yizhou Li, Yizhou Li
Abstract
Covalent 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.