Oligomer-guided recognition of two fucan sulfate from Bohadschia argus and inhibition of P-selectin binding to its ligand.

Dilihumaer Ruzemaimaiti, Huifang Sun, Jiali Zhang, Chen Xu, Linxia Chen, Ronghua Yin, Jinhua Zhao

Carbohydrate polymers 2023 Oct 01

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Fucan sulfate (FS) from sea cucumber shows intriguing structure and extensive activities. Here, three homogeneous FS (BaFSI - III) were obtained from Bohadschia argus, followed with physicochemical properties analyses including monosaccharide composition, molecular weight, and sulfate content. BaFSI was proposed to carry a unique distribution pattern of sulfate groups as a novel sequence composed of domain A and domain B that formed by different FucS residues, markedly differing from FS reported before, according to the analyses of 12 oligosaccharides and a representative residual saccharide chain. BaFSII possessed a highly regular structure {4-L-Fuc3S-α1,}n according to its peroxide depolymerized product. BaFSIII was confirmed as a FS mixture bearing similar structural characteristics with BaFSI and BaFSII by means of mild acid hydrolysis and oligosaccharide analysis. Bioactivity assays showed that BaFSI and BaFSII could potently inhibit P-selectin binding to PSGL-1 and HL-60 cells. Structure-activity relationship analysis showed that molecular weight and sulfation pattern were the essential factors for the potent inhibition. Meanwhile, an acid hydrolysate of BaFSII with a molecular weight about 15 kDa exhibited a comparable inhibition with the native BaFSII. Given the potent activity and highly regular structure of BaFSII, it shows great potential for development as a P-selectin inhibitor. Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Dilihumaer Ruzemaimaiti, Huifang Sun, Jiali Zhang, Chen Xu, Linxia Chen, Ronghua Yin, Jinhua Zhao. Oligomer-guided recognition of two fucan sulfate from Bohadschia argus and inhibition of P-selectin binding to its ligand. Carbohydrate polymers. 2023 Oct 01;317:121080