Abstract/Summary

Plant‐derived natural products (NPs) with electrophilic functional groups engage various subsets of the proteome via covalent modification of nucleophilic cysteine residues. This electrophile‐nucleophile interaction can change protein conformation, alter protein function, and modulate their biological action. The biological significance of these covalent protein modifications in health and disease is increasingly recognized. One way to understand covalent NP‐protein interactions is to utilize traditional proteomics and modern mass spectrometry (MS)‐based proteomic strategies. These strategies have proven effective in uncovering specific NP protein targets and are critical first steps that allow for a much deeper understanding of the ability of NPs to modulate cellular processes. Here, plant‐derived NPs that covalently modify proteins are reviewed, the biological significance of these covalent modifications, and the different proteomic strategies that have been employed to study these NP‐protein interactions.