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Heparin, an old but first-line anticoagulant, has been used over a century. It is a heterogeneous, linear, highly sulfated, anionic glycosaminoglycan with a broad distribution in relative molecular weight and charge density. These structural properties allow heparin to selectively interact with multiple proteins, leading to heparin's various pharmacological functions, such as anticoagulant, anti-viral, anti-tumor and anti-inflammatory activities. Clinical data suggest that unfractionated heparin or low molecule weight heparin could decrease mortality in COVID-19 patients with sepsis-induced hypercoagulation through the anticoagulant, anti-viral and anti-inflammatory activities of these drugs. Thus, the non-anticoagulant activity of heparin has again aroused attention. This review highlights recent advances in the preparation of heparin-derived drugs and clinical research on its non-anticoagulant properties over the past decade, to further the development and utilization of these important drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

Polyguluronic acid (PG) is a type of polysaccharide found in edible brown seaweeds. This study synthesized a new sulfated saccharide (SOGA) by sulfating PG-derived unsaturated oligoguluronic acid (OGA). The molecular weight and degree of sulfate-group substitution of SOGA were 1.6 kDa and 1.03, respectively. The structures of PG, OGA, and SOGA were elucidated using FT-IR and NMR spectroscopy. Furthermore, the immunomodulatory effects of PG, OGA, and SOGA on LPS-triggered RAW264.7 and BV2 cells were evaluated. SOGA, but not PG or OGA, significantly reduced the LPS-stimulated overproduction of proinflammatory mediators and suppressed the activation of corresponding signalling pathways. Also, SOGA could actively regulate immune balance by inhibiting apoptosis and pyroapoptosis. These results suggested that SOGA is a potential therapeutic agent for the prevention of diseases associated with immune disorders owing to its remarkable immunomodulatory effects, and that sulfate groups in the carbohydrate chain play a crucial role for its bioactivities. [Display omitted] [ABSTRACT FROM AUTHOR]

• A 1−6 glucanase was firstly used to digest a β-glucan from H. erinaceus. • The oligosaccharides in the digested products were analyzed with HPAEC-MS. • The sequences of enzyme resistant oligosaccharides were elucidated with MS/MS. • A branch-on-branch structure of the β-glucan was estimated. A water-soluble β-glucan from fruiting body of Hericium erinaceus was obtained after water extraction, purification and fractionation. Analyses of monosaccharide composition, molecular weight and linkage mode demonstrated that it is a β-glucan with 1→3 and 1→6 linkage modes and a molecular weight of 13.3 kDa. An endo-1,6-β- d -glucanase was used to digest the β-glucan and the digested products over time were analyzed with a HPAEC-PAD-MS platform. The linkage mode of each glycosidic bond in the digested oligosaccharides were confirmed with MS/MS. At the end of digestion, enzyme resistant oligosaccharides were observed as several 1→6 linked glucoses with one or two 1→3 linked glucose residues. All these domains are more like constructional pieces from a branch-on-branch glucan, in which multiple 1→6 linked glucan chains are hooked through one or two 1→3 linked glucose residues. Averagely, there is a 1→3 linkage per six 1→6 linked glucoses in this branch-on-branch β-glucan. [ABSTRACT FROM AUTHOR]

• Enzymatic depolymerization kinetics of chemically-modified heparin was analyzed. • Low molecular weight chemically-modified heparins were prepared and characterized. • The order of chemical modification and HepI lysis affected the product MW distribution. • LMW partially 6- O -/ N -desulfated heparin suppressed bleomycin-induced cell apoptosis. Non-anticoagulant biological functions of heparin-based drugs have drawn increasing attention. However, the exploration into the non-anticoagulant activities of various low molecular weight heparins was associated with bleeding risks in clinical practice and often led to controversial conclusions due to the structural differences. In this study, we aimed to establish a process to produce a library of heparin derivatives with structural diversity and reduced/abolished anticoagulant activity through the combination of chemical modifications and enzymatic cleavage of heparins. The depolymerization characteristics of various selectively modified heparin derivatives by three heparinases were comprehensively analyzed. The order of periodate treatment and heparinase-I depolymerization was proved to significantly change the structural characteristics of the oligosaccharide products. Finally, among several heparin derivatives that screened in the bleomycin-induced cell apoptosis model, the low molecular weight partially 6- O- / N -desulfated heparins showed the strongest anti-apoptotic activities. This study provided a useful approach for future development of novel heparin-derivative medications. [ABSTRACT FROM AUTHOR]