Section Review: Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: Therapeutic regulation of 14 kDa phospholipase A2(s)

Phospholipases A2(s) (PLA2), which catalyse the hydrolysis of the sn-2 fatty acyl chain of phospholipid substrates to yield fatty acids and lysophospholipids, have over the last few years become a broad group of structurally and mechanistically diverse enzymes. The importance and respective functions of the various PLA2 isoforms are only now beginning to be appreciated. The type II 14 kDa PLA2 is clearly implicated in disease states and, as such, has been a prime target for therapeutic intervention; while the biological function of the 85 kDa PLA2 is not fully understood. The 14 and 85 kDa PLA2 enzymes are structurally and mechanistically distinct and, as such, development of selective 14 kDa PLA2 inhibitors has been achieved. Herein, the structural aspects and biological role of the type II 14 kDa PLA2 are reviewed and compared with the 85 kDa PLA2 to define better their respective roles. Further, the more recent chemical strategies for designing 14 kDa PLA2 inhibitors are reviewed and key compounds summ...