Structure versus anticoagulant and antithrombotic actions of marine sulfated polysaccharides

Abstract

Marine sulfated polysaccharides (MSP), such as sulfated fucans (SF), sulfated galactans (SG) and glycosaminoglycans (GAG) isolated from either algae or invertebrate animals, are highly anionic polysaccharides capable of interacting with certain cationic proteins, such as (co)-factors of the coagulation cascade during clotting-inhibition processes. These molecular complexes between MSP and coagulation-related proteins might, at first glance, be assumed to be driven mostly by electrostatic interactions. However, a systematic comparison using several novel sulfated polysaccharides composed of repetitive oligosaccharides with clear sulfation patterns has shown that these molecular interactions are regulated essentially by the stereochemistry of the glycans (which depends on a conjunction of anomericity, monosaccharide, conformational preference, and glycosylation and sulfation sites), rather than just a simple consequence of their negative charge density (mainly the number of sulfate groups). Here, we present an overview of the structure-function relationships of MSP, correlating their structures with their potential anticoagulant and antithrombotic actions, since pathologies related to the cardiovascular system are one of the major causes of illness and mortality in the world.

Anticancer and Cancer Preventive Properties of Marine Polysaccharides: Some Results and Prospects

“…They contain a great variety of polysaccharide compounds, including glycosaminoglycans, fucans, and galactans [ 23 , 128 , 129 , 130 ]. These compounds demonstrate diverse biological properties, including anticoagulant and antitrombotic [ 131 , 132 , 133 ], antioxidative [ 134 ], neuroprotective [ 135 , 136 ], and antiviral activity as well [ 8 , 137 ]. However, anticancer and cancer preventive activities of the polysaccharides from marine animals have been studied insufficiently.…”

Antithrombotics from the Sea: Polysaccharides and Beyond

“…Until 2014, several examples of structurally unique GAGs with anticoagulant and antithrombotic effects isolated from ascidians [53,54,55,56,57], sea urchins [58], sea cucumbers [51,59,60,61], mollusks [62], and shrimps [63,64] were described in the literature. The main feature of these new and interesting GAGs isolated from the extracellular matrices of certain marine invertebrates is the structural regularity that, contrary to mammalian GAGs, allows the development of advanced structure–anticoagulation relationship studies [17,19,51,60]. The main conclusions of these studies point out the importance of specific structural combinations, such as the 2,4-di-sulfation with α- l -Fucp units found in the branched FCS molecules from sea cucumbers or the combination of the 4-sulfation in GalNAc units with occasional 2-sulfation in IdoA, as is the case of DS from ascidians (Figure 5) [17,51].…”

“…The reasons for the growing interest in these molecules consist of (1) substantially lower contamination levels of virus and/or prions, since they are exclusively extracted from marine sources [19]; (2) the unique and distinct structures of these glycans compared to the GAG structure [24,132]; (3) the mechanisms of action that, although being similar to the GAGs used in medicine, can exhibit additional or slightly different effects, which can be considered advantageous factors in the development of alternative anticoagulants [13]; (4) the fact that some SFs and SGs do not exhibit bleeding risks, contrarily to the HP therapy [133]. In general, algal polysaccharides are structurally more complex, with heterogeneous structures, compared to polysaccharides isolated from marine invertebrates that have simple, linear structures [134].…”

“…While comprehensive and updated reviews can be found in the literature regarding marine sulfated polysaccharides with antithrombotic activities [9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31], reports of marine antithrombotic small molecules are still sparse in the literature. Therefore, we performed a run-up review of some of the major representatives and newest examples of bioactive polysaccharides reported in the last five years, and a systematic compilation of small molecules isolated from marine organisms with antithrombotic activities.…”

Specific sulfation and glycosylation—a structural combination for the anticoagulation of marine carbohydrates

“…Based on comparative and systematic analyses on the structure-anticoagulation relationships of certain MSPs, we noticed that to achieve a good anticoagulant response, certain structural combinations of sulfation and glycosylation are indeed required. In these analyses, we have particularly given more preference to examine SFs, SGs and GAGs from marine invertebrates or red algae, since these organisms can provide molecules of well-defined chemical structures (Mourão, 2004 ; Pomin, 2009 , 2012c ; Pomin and Mourão, 2012 ). This kind of structural regularity has facilitated interpretation and this in turn enables us to establish advanced structure-anticoagulation relationships (Pereira et al, 2002 ; Pomin, 2009 , 2012c ).…”