Activated Ketones as Inhibitors of Intracellular Ca2+-Dependent and Ca2+-Independent Phospholipase A2

摘要: Studies are reported on two different types of activated ketones as inhibitors important intracellular phospholipase A2s (PLA2):  the group IV 85 kDa Ca2+-dependent A2 (cPLA2) and P388D1 Ca2+-independent (iPLA2). In a mixed micelle assay, we observed that reaction progress curve cPLA2 in presence trifluoromethyl ketone (TFMK) is linear at pH 7.4, while 9.0 it nonlinear slows with time. An investigation this discrepancy demonstrated TFMKs slow, tight-binding both pH's, rate dissociation enzyme−inhibitor complex same but association enzyme inhibitor slower 7.4 than 9.0. A novel has been synthesized contain fatty acyl tricarbonyl. These compounds also inhibit assay. The inhibition by tricarbonyls readily reversible upon dilution ...