Quinones, produced by the oxidation of phenolic compounds, are highly reactive electrophiles. Theyreadily react with nucleophilic groups of proteins or free amino acids to form quinone-protein orquinone-amino acid adducts. The products of the reaction between 4-methylbenzoquinone (4MBQ)and β-lactoglobulin (β-LG)/free amino acids were identified. LC-MS-based proteomic analysisrevealed that Cys on β-LG was the most modified residue when reacted with 4MBQ at neutral pH.The product corresponding to Michael addition was identified in all reactions of 4MBQ with freeamino acids. The formation of Schiff base and di-adduct was found in His, Trp and Lys samples.Moreover, NMR analysis proved that Michael addition occurred on the C5 position of 4MBQ whenreacted with Nα-acetyl-Lys. To comprehensively reveal the reactivity of quinone towards proteinsand amino acids, kinetics studies were included. The reactivity of 4MBQ with different proteins wasdependent on the availability of thiol groups. The rate of reactions decreased in the order: β-LG >His > Trp ~ Lys > Arg > Nε-acetyl-Lys > Nα-acetyl Lys > Nα-acetyl His > Nα-acetyl Arg > Nα-acetylTrp. In addition, the rate constants correlated with the pKa values of the amino acids. The kineticsresults showed that temperature dependence followed the Arrhenius law in the range of 15-45 ºC withactivation energies in the order: Lys < Nε-acetyl Lys < Nα-acetyl Lys. The nature of products was notaffected by temperature in the range of 15-100 ºC.The bioactivities of the digests derived from the adduct of 4MBQ with β-LG were evaluated in LPS-induced RAW 264.7 cells. The fraction over 3 kDa of digests suppressed the production of IL-6 andTNF-α. The digests also exhibited cellular antioxidant activity, which is likely due to the presence ofantioxidant peptides and the antioxidant activity of the parent phenolic compound. To investigate therole of commonly found phenolic compounds in the food system, the immunomodulatory effects ofcaffeic acid-Cys and chlorogenic acid-Cys adduct were the first studied in RAW264.7 cells. RNA-sequencing showed that the Toll-like receptor signaling pathway, chemokine signaling pathways andNOD-like receptor signaling pathways, JAK-STAT and MAPK signaling pathways were upregulatedin adduct-treated cells compared to the parent phenolic compound. Productions of PGE2 and TNF-αwere further suppressed by adduct-stimulated cells compared to the parent phenolic compound-stimulated cells, but ROS production was increased. Collectively, the addition of Cys moiety intophenolic compounds drastically alters the anti-inflammatory activity. These results together indicatethat the covalent bond between quinones and proteins/amino acids) alters the biological activities ofthe parent proteins/amino acids or phenolic compounds.