DNA‐templated Photo‐crosslinking for Library Selection and Target Identification

Abstract

Sensitive and specific labelling of small‐molecule‐binding proteins is of high significance in chemical biology and drug discovery. We have developed a novel method named DNA-programmed Photo‐Affinity Labelling (DPAL). DPAL’s unique dual‐probe system provides simple, flexible and modular affinity labelling of small molecule’s protein targets. Importantly, the introduction of DNA encoding and template effect enable multiplexed protein labelling by multiple probes in a single solution. We show that DPAL can be implemented in the selection of DNA‐encoded chemical libraries directly against soluble protein targets, as well as in target identification of bioactive small molecules.