Chemical structure and P-selectin inhibition of two linear and highly regular homofucans from the brown alga Fucus vesiculosus.

Fucoidan from Fucus vesiculosus is historically significant but possesses a highly heterogeneous structure that has long obscured its precise chemical nature and structure-activity relationships (SAR). In this study, two homofucans, FS-I and FS-II (at a weight ratio of 1:2.7), were purified from commercial F. vesiculosus fucoidan via fractional ethanol precipitation and ion-exchange chromatography. Comprehensive 1D/2D NMR analysis of the native polymers, their peroxidative depolymerized products, and oligosaccharides from acid hydrolysis established that both are highly ordered linear polymers with predominantly alternating α1,3 and α1,4 glycosidic linkages. FS-II consists of the repeating unit -{L-Fuc2S-α1,4-L-Fuc2S3S-α1,3}-, while FS-I was identified as a novel, naturally occurring fully sulfated fucan with the repeating unit -{L-Fuc2S4S-α1,4-L-Fuc2S3S-α1,3}-. Biological evaluation demonstrated that both exhibit potent and comparable P-selectin inhibitory activities. SAR analysis revealed that FS-II slightly outperformed FS-I at an equivalent degree of polymerization, suggesting that the O-4 sulfate groups in FS-I should not be necessary for P-selectin inhibition. Furthermore, depolymerization effectively decoupled the potent inhibitory activity from the unwanted platelet activation effects seen in high-molecular-weight fractions. Specifically, low-molecular-weight FS-II (e.g., 24.76 kDa) may serve as a promising lead for the development of safer P-selectin inhibitor.