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Updated: Jul 16, 2025
Genome-wide Mapping of Drug-DNA Interactions in Cells with COSMIC Crosslinking of Small Molecules to Isolate Chromatin
Published on: January 20, 2016
Covalent Capture and Selection of DNA-Encoded Chemical Libraries via Photo-Activated Lysine-Selective Crosslinkers
Haimei Wei1, Tianyang Zhang1, Yangfeng Li1,2
1Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Innovative Drug Research Center, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, P. R. China.
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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