Anticoagulant and Antithrombotic Properties of Three Structurally Correlated Sea Urchin Sulfated Glycans and Their Low-Molecular-Weight Derivatives

Abstract

The anticoagulant and antithrombotic properties of three structurally correlated sea urchin-derived 3-linked sulfated α-glycans and their low molecular-weight derivatives were screened comparatively through various in vitro and in vivo methods. These methods include activated partial thromboplastin time, the inhibitory activity of antithrombin over thrombin and factor Xa, venous antithrombosis, the inhibition of platelet aggregation, the activation of factor XII, and bleeding. While the 2-sulfated fucan from Strongylocentrotus franciscanus was observed to be poorly active in most assays, the 4-sulfated fucan from Lytechinus variegatus, the 2-sulfated galactan from Echinometra lucunter and their derivatives showed multiple effects. All marine compounds showed no capacity to activate factor XII and similar low bleeding tendencies regardless of the dose concentrations used to achieve the highest antithrombotic effect observed. The 2-sulfated galactan showed the best combination of results. Our work improves the background about the structure-function relationship of the marine sulfated glycans in anticoagulation and antithrombosis. Besides confirming the negative effect of the 2-sulfated fucose and the positive effect of the 2-sulfated galactose on anticoagulation in vitro, our results also demonstrate the importance of this set of structural requirements on antithrombosis in vivo, and further support the involvement of high-molecular weight and 4-sulfated fucose in both activities.

Marine Antithrombotics

“…This suggested a plausible role for the nature of sugar on the observed activity, as shown in Table 6 . The study reaffirms the role of molecular weight and sulfation pattern to be critical in antithrombotic and anticoagulant activity, as observed in many previous studies [ 89 ].…”

Antithrombotics from the Sea: Polysaccharides and Beyond

“…The tail vein of the mouse was wounded, and the blood was absorbed into a filter paper every 1.5 s. Bleeding time can be calculated at the point in which no blood is detected on the paper (performed for plancinin in Section 3.2.1) [46]. The bleeding time (see for example urchin sulfated glycans in Section 3.1) can also be evaluated by immersing the tail in water and following that, hemoglobin is measured by spectrophotometry [47].…”

“…The inferior vena cava was isolated, and different doses of the test compounds were infused and allowed to circulate for 5 min. Then, the formed thrombus was removed and weighed and compared with the thrombus weight in the absence of analyte administration [47].…”

“…The marine environment is also a rich source of structurally unique GAGs, known as GAG mimetics, such as SFs and SGs isolated from certain macroalgae (brown [31,34,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90], red [91,92,93,94,95,96,97,98,99,100,101,102,103], and green [72,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118] (Figure 7)), microalgae [119,120,121] or from invertebrates [47,58,65,122,123,124,125,…”

Chondroitin Sulfate-Degrading Enzymes as Tools for the Development of New Pharmaceuticals

“…Recently, the preparation of low molecular weight fucosylated chondroitin sulfates (LMWfCSs) has attracted much attention [106] (Figure 8). Fucosylated CSs (fCSs) are CSs with fucose branches invariably extending from the 3-O-position of the GlcA.…”