Reactivity of Lysine Moieties toward γ-Hydroxy-α,β-unsaturated Epoxides: A Model Study on Protein−Lipid Oxidation Product Interaction

Epoxyols are generally accepted as crucial intermediates in lipid oxidation. The reactivity of γ-hydroxy-α,β-unsaturated epoxides toward lysine moieties is investigated, employing trans -4,5-epoxy- trans -2-hexen-1-ol (EH) as a model substrate and propylamine or N 2 -acetyl- l -lysine 4-methylcoumar-7-ylamide (AcLys-MCA) as model reagents for protein-bound lysine. Independent syntheses are reported for EH and AcLys-MCA. Reaction of the amine components with EH in THF yields 4-(propylamino)- trans -2-hexene-1,5-diol and N 2 -acetyl- N 6 -(1,5-dihydroxy- trans -2-hexen-4-yl)- l -lysine 4-methylcoumaryl-7-amide, respectively. Unequivocal structural characterization of the products prove the epoxy ring cleavage to proceed by a true S N 2 mechanism. Incubation of EH with propylamine and AcLys-MCA in aqueous medium at 37 °C shows the turnover to decrease with lower pHs. From reaction of EH (100 mM) with AcLys-MCA (50 mM) under physiological conditions (pH 7.4), 3% of the lysine moieties can be identified in the form of N 2 -acetyl- N 6 -(1,5-dihydroxy- trans -2-hexen-4-yl)- l -lysine 4-methylcoumar-7-ylamide after 24 h.