– 4-Oxo-2-nonanal (4-ONE) is a lipid peroxidation product that actively modifies histidine and lysine residues in proteins, leading to protein cross-linking, and alters 2′-deoxyguanosine, indicating its role in mutagenesis and carcinogenesis. 4-ONE alkyne, an alkyne-tagged electrophile, serves as a probe for isolating and identifying lipid peroxidation reaction products through click chemistry.