Synthesis of phospholipids on a glyceric acid scaffold: design and preparation of phospholipase A2 specific substrates

TETRAHEDRON

卷:70

Article

Hajdu, Joseph¹ 

[1] Calif State Univ Northridge, Dept Chem & Biochem, Northridge, CA 91330 USA

关键词: Phospholipid synthesis;    Glyceric acid;    Phospholipase A(2) activity-probe;    Reporter group;   

DOI  :  10.1016/j.tet.2014.03.054

来源: Elsevier

【 摘 要 】

Synthesis of a new series of phospholipid analogues to serve as activity-based probes of secretory phospholipase A(2) enzymes is reported. The synthesis is based upon (1) preparation of long-chain esters and amides of glyceric acid, followed by (2) regioselective derivatization of the diol function of the molecule to achieve phosphorylation at the primary hydroxyl group, and to introduce the incipient sn-2-ester group of the target compounds. The sequence has been shown to allow incorporation of fluorescent, paramagnetic, and redox-active reporter groups, leading to phospholipid analogues applicable to detect and measure enzyme activity, to develop highly specific, real-time spectroscopic assay of phospholipase A(2) enzymes, as well as to track the metabolic fate of the hydrolysis products. The synthetic method has a great deal of flexibility to open the way to the design and synthesis of activity-probes for other phospholipid metabolizing enzymes as well. (c) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

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