摘要
Free radical depolymerization has been widely employed for polysaccharide structural and functional studies. However, H 2 O 2 -induced depolymerization of the unique sea cucumber derived fucosylated chondroitin sulfate (FCS) generated diverse fragments with oxidation at their reducing ends, thus limiting preparation of well-defined oligosaccharides. Here, a thermal dissociation initiator, potassium persulfate (KPS), was utilized to induce radical depolymerization of FCS, leading to depolymerized products that maintained their basic structural units and sulfate substituents. Structural analysis of the resulting oligosaccharides revealed that the reducing ends were uniformly GalNAc 4S6S acid, distinct from those generated by H 2 O 2 -induced FCS depolymerization. The major components, tetrasaccharide (FIIIa), heptasaccharide (FVa) and decasaccharide (FVIa) possessed GalNAc 4S6S residues at their non-reducing ends, demonstrating that the D-GlcA-β1,3-D-GalNAc 4S6S linkage was preferentially cleaved. A free radical depolymerization mechanism of FCS by KPS was proposed. The regular aldonic acid terminal formation was attributed to the strong oxidative capacity of the sulfate radical for extensive oxidation of the newly formed GlcA residue after β1,3 glycosidic linkage cleavage, and further oxidation of C-1 of GalNAc. KPS was thermally dissociated to generate sulfate radicals, which subsequently attacked FCS chains and led to their fragmentation. Moreover, biological activity assay showed that heptasaccharide FVa and decasaccharide FVIa demonstrated strong anticoagulant activity, primarily via iXase inhibition mediated by high-affinity interaction with FIXa. Intriguingly, the unique oxidized reducing end exhibited enhanced iXase inhibitory activity. Hence, our findings expanded the free radical depolymerization of FCS and enriched structure-activity relationship information for iXase inhibition.
危险品化学品经营许可证（带存储）