Design, synthesis of ceramide 1-phosphate analogs and their affinity for cytosolic phospholipase A2 as evidenced by surface plasmon resonance

Abstract

Ceramide 1-phosphate (C1P) is a lipid mediator that specifically binds and activates cytosolic phospholipase A₂α (cPLA₂α). To elucidate the structure-activity relationship of the affinity of C1P for cPLA₂α in lipid environments, we prepared a series of C1P analogs containing structural modifications in the hydrophilic parts and subjected them to surface plasmon resonance (SPR). The results suggested the presence of a specific binding site for cPLA₂α on the amide, 3-OH and phosphate groups in C1P structure. Especially, dihydro-C1P exhibited enhanced affinity for cPLA₂α, suggesting the hydrogen bonding ability of 3-hydroxy group is important for interactions with cPLA₂α. This study helps to understand the influence of specific structural moieties of C1P on the interaction with cPLA₂α at the atomistic level and may lead to the design of drugs that regulate cPLA₂α activation.

Keywords: Ceramide 1-phosphate; Cytosolic phospholipase A(2)α; Lipid-protein interaction; Surface plasmon resonance.