Biologically active synthetic phospholipid compounds are required for structural and dynamic studies of biomembranes to establish structure-activity relationships with respect to phospholipid-phospholipid and phospholipid-protein interactions, as well as for mechanistic elucidation of phospholipid metabolizing enzymes. A significant number of mammalian phospholipases are secreted enzymes, found in specific tissues and cellular locations, exhibiting unique enzymatic properties and distinct biological functions. We have designed a series of double-labeled mixed-chain phospholipid analogues with chain-terminal coumarin fluorophores for fluorescence resonance energy transfer (FRET)-based real-time kinetic studies of phospholipase A2 (PLA2) enzymes. Coumarin derivatives as fluorescent labels provide reporter groups with significantly smaller size than fluorophores previously used in donor-acceptor pairs, and interfere less with the physicochemical properties of the acyl chains of phospholipids. The synthetic probes include phospholipids with structurally modified hydrolysis resistant sn-1-substituents, and intact sn-2-ester groups to achieve selectivity for PLA2 enzymes. Details of the syntheses and formation of the hydrolysis products will be presented.

Synthesis of functionalized phospholipid analogs for kinetic and mechanistic studies of lipolysis by phospholipase A<sub>2</sub> enzymes

246th National Meeting (2013)

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Synthesis of functionalized phospholipid analogs for kinetic and mechanistic studies of lipolysis by phospholipase A2 enzymes

Synthesis of functionalized phospholipid analogs for kinetic and mechanistic studies of lipolysis by phospholipase A₂ enzymes