Glycosaminoglycans analogs from marine invertebrates: structure, biological effects, and potential as new therapeutics

Abstract

In this review, several glycosaminoglycan analogs obtained from different marine invertebrate are reported. The structure, biological activity and mechanism of action of these unique molecules are detailed reviewed and exemplified by experiments in vitro and in vivo. Among the glycans studied are low-sulfated heparin-like polymers from ascidians, containing significant anticoagulant activity and no bleeding effect; dermatan sulfates with significant neurite outgrowth promoting activity and anti-P-selectin from ascidians, and a unique fucosylated chondroitin sulfate from sea cucumbers, possessing anticoagulant activity after oral administration and high anti P- and L-selectin activities. The therapeutic value and safety of these invertebrate glycans have been extensively proved by several experimental animal models of diseases, including thrombosis, inflammation and metastasis. These invertebrate glycans can be obtained in high concentrations from marine organisms that have been used as a food source for decades, and usually obtained from marine farms in sufficient quantities to be used as starting material for new therapeutics.

Non-Anticoagulant Heparins as Heparanase Inhibitors

“…The composition of natural physiological HS chains can be altered in several pathological conditions [8][9][10][11]. Heparin and HS-like glycosaminoglycans (GAGs) have been isolated from avian intestinal mucosa [12], terrestrial invertebrates [13,14], marine crustacean and mollusk species [15][16][17] as well as bacterial and virus species [12]. In the Golgi compartment of all animal cells and mast cells of connective tissue, biosynthesis of HS and heparin chains, respectively are completed through common steps leading to the formation of a specific tetrasaccharidic linkage region…”

“…The highly sulfated domains (NS), constituted by sequences of the trisulfated disaccharide 4-O-L-IdoA2S 1α-4-O-D-GlcNS6S are prevalent in heparin chains, while in the N-acetylated domains (NA), the disaccharide 4-O-α-D-GlcA-1β-4-O-D-GlcNAc) is more abundant in HS chains. NS and NA domains in both HS and heparin are disseminated among mixed transition regions (NS/NA) [9][10][11][12][13][14][15][16][17][18].…”

Anti-Obesity Effect of Bombus ignitus Queen Glycosaminoglycans in Rats on a High-Fat Diet

“…Glycosaminoglycans (GAGs), including heparin-like polymer, that are derived from vertebrates have diverse pharmacological activities including anticoagulant, antithrombotic, and anti-inflammatory activities [1]. GAGs isolated and purified from various vertebrate and invertebrate tissues have been shown to comprise of an anion sugar sulfate with functional properties [2].…”

Heparan sulfate/heparin glycosaminoglycan binding alters inhibitory profile and enhances anticoagulant function of conserved Amblyomma americanum tick saliva serpin 19

“…Kim et al, (2016a) showed that RNAi silencing of AAS19 caused deformities in ticks suggesting that this serpin regulated an important protease in the tick. There is evidence that invertebrates do produce heparin-like GAGs (Chavante et al, 2014; Pavão, 2014). It will be interesting to investigate if tick derived GAGs affected inhibitory functions of native AAS19 in the tick.…”