Structure-inspired design of a sphingolipid mimic sphingosine-1-phosphate receptor agonist from a naturally occurring sphingomyelin synthase inhibitor.

Chem Commun (Camb) 2018 Nov;54(90):12758-12761

Graduate School of Life Science, Hokkaido University, Kita 21 Nishi 11, Sapporo 001-0021, Japan.

Ginkgolic acid obtained as a sphingomyelin synthase inhibitor from a plant extract library inspired the concept of sphingolipid mimics. Ginkgolic acid-derived N-acyl anilines and ginkgolic acid 2-phosphate (GA2P) respectively mimic ceramide and sphingosine 1-phosphate (S1P) in structure and function. The GA2P-induced phosphorylation of ERK and internalization of S1P receptor 1 (S1P1) indicated potent agonist activity. Docking studies revealed that GA2P adopts a similar binding conformation to the bound ligand ML5, which is a strong antagonist of S1P1.

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http://xlink.rsc.org/?DOI=C8CC05595E
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http://dx.doi.org/10.1039/c8cc05595eDOI Listing
November 2018
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