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Seven macromolecular polysaccharides (HPP-2S−HPP-8S) were purified from the gonads of sea urchin Hemicentrotus pulcherrimus. They were characterized as α-glucan homologues, sharing the same α-1,4-glucan backbone substituted at C-6 positions by glucose with HPP-1S that occurs as the major polysaccharide in H. pulcherrimus , while with higher degrees of branching, and additionally possessing minor amounts of mannose and ribose. The branching degree and amounts of non-glucose branches showed a generally increasing tendency across HPP-2S − HPP-8S. These polysaccharides exhibited significant macrophage-activating effects by augmenting the secretion of NO, TNF-α and IL-6, which probably involves the activation of NF-κB and MAPKs signaling pathways. Notably, the polysaccharides with a higher degree of branching exhibited markedly enhanced immunomodulatory capacity with a lowest effective concentration of 1.95 μg/mL. This work provides new cases of bioactive α-glucans and reveals their potential application as immunomodulating agents. • Seven new polysaccharides were isolated from Hemicentrotus pulcherrimus. • They were characterized as α-1,4-glucan homologues with varying degrees of branching. • The α-1,4-glucan with a higher degree of branching showed more potent stimulatory effect on macrophage. • HPP-6S could activate macrophage at a low concentration of 1.95 μg/mL. [ABSTRACT FROM AUTHOR]

Aldolase A (ALDOA) promotes hepatocellular carcinoma (HCC) growth and is a potential therapeutic target. A previous study found an α-D-glucan (α-D-(1,6)-Glc p -α-D-(1,4)-Glc p , 10.0:1.0), named HDPS-4II, that could specifically inhibit ALDOA but its activity was not high enough. In this study, the derivatives of α-D-glucan binding to ALDOA were optimized using molecular docking, and its sulfated modification demonstrated the highest affinity with ALDOA among sulfated, carboxylated, and aminated derivatives. Sulfated HDPS-4II and dextrans with different molecular weights (1000 Da, 3000 Da, and 4000 Da) were prepared. Using MST assay, 3- O -sulfated HDPS-4II (SHDPS-4II) and 1000 Da dextran (SDextran1) showed higher affinities to ALDOA with K d of 1.83 μM and 85.04 μM, respectively. Furthermore, SHDPS-4II and SDextran1 markedly inhibited the proliferation of HCC cells both in vitro and in vivo by blocking ALDOA. These results demonstrate that sulfated modification of α-D-glucans could enhance their affinities with ALDOA and anti-HCC effects. [Display omitted] [ABSTRACT FROM AUTHOR]