Global identification of the cellular targets for a multi-molecule system by a photochemically-induced coupling reaction

Abstract

Current target identification strategies mainly focus on single compounds. However, no practical experimental methodologies have been developed for multi-molecule systems. Herein, we established a cellular target identification technology for a multi-molecule system by preparing 4,4′-dihydroxybenzophenone (DHBP)-bound Fe₃O₄ nanoparticles (NPs) with photochemically induced crosslinking capacity. DHBP-bound NPs reacted with the chemicals from the medicinal plant extract as a multi-molecule system under ultraviolet radiation by forming carbon–carbon bonds, thus generating extract-crosslinked NPs for capturing target proteins from cell lysates. The technology, which is named the Zhao-Yao (ZY) strategy, may promote the comprehensive interpretation of the pharmacological mechanism of multi-molecule systems via the global identification of cellular targets.