REACTIVITY OF LYSINE MOIETIES TOWARD GAMMA-HYDROXY-ALPHA,BETA-UNSATURATED EPOXIDES - A MODEL STUDY ON PROTEIN-LIPID OXIDATION PRODUCT INTERACTION

摘要

Epoxyols are generally accepted as crucial intermediates in lipid oxidation. The reactivity of gamma-hydroxy-alpha,beta-unsaturated epoxides toward lysine moieties is investigated, employing trans-4,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 bf EH with propylamine and AcLys-MCA in aqueous medium at 37 degrees 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.