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.
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