Description
Phospholipase A
2 (PLA
2) 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 PLA
2 exist: secretory (sPLA
2), calcium-
dependent cytosolic (cPLA
2), and calcium-
independent cytosolic (iPLA
2).
2 Of these three enzymes, cPLA
2 is the rate-
limiting stimulus for release of arachidonic acid whereas sPLA
2 amplifies the action of cPLA
2 and regulates phagocytosis and foam cell formation.
3 CAY10590, a simple amide based on (R)-
γ-
norleucine, is a potent and selective inhibitor of sPLA
2. It exhibits 95% inhibition (X
I(50) = 0.003) of sPLA
2 at 0.091 mole fraction without affecting the activities of cPLA
2 or iPLA
2.
4
References
1. Dennis, E.A.
Phospholipases The Enzymes XVI,(1983).
2. Dennis, E.A.
Diversity of group types, regulation, and function of phospholipase A2 J. Biol. Chem. 269,13057-13060(1994).
3. Balestrieri, B., and Arm, J.P.
Group V sPLA2: Classical and novel functions Biochim. Biophys. Acta 1761,1280-1288(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. Chem. 16,10257-10269(2008).
