Carbohydr Polym 2025 Feb 01;355:123351. doi: 10.1016/j.carbpol.2025.123351.

Unique structure and biological properties of fucosylated glycosaminoglycan and its oligosaccharides from sea cucumber Holothuria floridana.

???displayArticle.abstract???
Fucosylated glycosaminoglycan (FG) from Holothuroidea exhibits notable structural diversity and multiple biological activities. This study investigated the HfFG isolated from the sea cucumber Holothuria floridana, focusing on its chemical structure and biological activities. Structural analysis of eleven oligosaccharides (a-k) and a depolymerized product (dHfFG-II) using NMR identified the HfFG backbone as chondroitin sulfate E (CS-E), with various branches, including L-Fuc2S4S, L-Fuc3S4S, L-Fuc4S, and the unique disaccharide D-GalNAc4S-α1,2-L-Fuc3S4S, attached at C-3 of GlcA. A high L-Fuc2S4S (40 %) and disaccharide branch (35 %) content allowed their contiguous distribution within the CS-E chain, as evidenced by the predominant hexasaccharides (i, j) in size-homogeneous Fr4 and the novel nonasaccharide k in Fr5. Notably, previously unreported branches and sequences in HfFG were confirmed, offering new understanding of the natural HfFG structure. HfFG showed potent inhibitory activities on the intrinsic tenase complex (iXase), heparanase, and P-selectin binding to PSGL-1. Depolymerization selectively modulated these activities, preserving anti-iXase potency while attenuating heparanase and P-selectin inhibition. These activities were dependent on oligosaccharide chain length and sequence. Comparing the activities of FG and its oligosaccharides highlights their potential for the rational design of targeted inhibitors of heparanase or P-selectin binding to PSGL-1, with significant implications for therapeutic applications.

???displayArticle.pubmedLink??? 40037731
???displayArticle.link??? Carbohydr Polym