Phospholipase A2 (PLA2) catalyzes the hydrolysis of fatty acids at the sn-2 position of glycerophospholipids, liberating arachidonic acid for subsequent eicosanoid synthesis.1 Three primary types of PLA2 exist: secretory (sPLA2), calcium-dependent cytosolic (cPLA2), and calcium-independent cytosolic (iPLA2).2 Of these three enzymes, cPLA2 is the rate-limiting stimulus for release of arachidonic acid whereas sPLA2 amplifies the action of cPLA2 and regulates phagocytosis and foam cell formation.3 CAY10590, a simple amide based on (R)-γ-norleucine, is a potent and selective inhibitor of sPLA2. It exhibits 95% inhibition (XI(50) = 0.003) of sPLA2 at 0.091 mole fraction without affecting the activities of cPLA2 or iPLA2. 4
2
Dennis, E.A. Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem26913057-13060(1994).
3
Balestrieri, B., and Arm, J.P. Group V sPLA2: Classical and novel functions. Biochim Biophys Acta17611280-1288(2006).
4
Antonopoulou, G., Barbayianni, E., Magrioti, V., et al. Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A2 enzymes. Bioorg Med Chem1610257-10269(2008).
Dennis, E.A. Diversity of group types, regulation, and function of phospholipase A2. J Biol Chem26913057-13060(1994).
Antonopoulou, G., Barbayianni, E., Magrioti, V., et al. Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A2 enzymes. Bioorg Med Chem1610257-10269(2008).
Balestrieri, B., and Arm, J.P. Group V sPLA2: Classical and novel functions. Biochim Biophys Acta17611280-1288(2006).