Solid-phase synthesis of polyunsaturated fatty acids facilitates precise structural investigation on FFAR1/4 agonist activities and the inhibition of neutrophil pseudopod formation.

Polyunsaturated fatty acids (PUFAs), fatty acids with multiple unsaturated carbon-carbon bonds, constitute a crucial class of lipids. While the vast diversity of PUFA species arises from their structural variations, most of them are poorly investigated due to their limited availability. Here, we utilize solid-phase synthesis of PUFAs, which we have recently developed, to construct a PUFA library. With the library, we investigate agonist activities for free fatty acid receptors 1 (FFAR1) and 4 (FFAR4), inhibition abilities against neutrophil pseudopod formation, and anti-inflammatory effects on the hypersensitivity mouse model. This study highlights the utility of PUFA solid-phase synthesis as a powerful approach for elucidating the relationship between the chemical structures of PUFAs and their biological functions.