Selective sulfation of carrageenans and the influence of sulfate regiochemistry on anticoagulant properties

Abstract

Sulfated polysaccharides are recognized for their broad range of biological activities, including anticoagulant properties. The positions occupied by the sulfate groups are often related to the level of the inherent biological activity. Herein the naturally sulfated galactans, kappa-, iota- and theta-carrageenan, were additionally sulfated by regioselective means. The anticoagulant activity of the resulting samples was then studied using the aPTT in vitro assay. The influence of sulfate regiochemistry on the anticoagulant activity was evaluated. From kappa-carrageenan three rare polysaccharides were synthesized, one of them involved a synthetic route with an amphiphilic polysaccharide intermediate containing pivaloyl groups. Iota- and theta-carrageenan were utilized in a selective C6 sulfation at β-D-Galp units to produce different structures comprising trisulfated diads. All the samples were characterized by NMR (1D and 2D). The resulting aPPT measurements suggested that sulfation at C2 of 3,6-anhydro-α-D-Galp and C6 of β-D-Galp increased the anticoagulant activity.

Regioselective sulfation of Artemisia sphaerocephala polysaccharide: Characterization of chemical structure

“…Therefore, new synthetic methods have to be developed for regionselective modification. Several publications have shown the interest in modified polysaccharides with different substitution positions by using regioselective synthesis, including glycosaminoglycan (Redouan et al, 2012), curdlan (Zhang & Edgar, 2014), amylase (Shen, Ikai, & Okamoto, 2010) and carrageenans (Araújo et al, 2013). Nishimura et al report that the chitin and chitosan derivative using selective sulfation at C-2 and/or C-3 affords greater anti-AIDS activities than that by the known C-6 sulfated derivative in vitro.…”

Formation of κ-carrageenan–gelatin polyelectrolyte complexes studied by 1H NMR, UV spectroscopy and kinematic viscosity measurements

“…κ-Carrageenan, which is rich in natural resources, is obtained from red algae (Rhodophyta), mainly from Kappaphycus alverezii (Cottonii) (Imeson, 2009;Jiao, Yu, Zhang, & Ewart, 2011). This type of polysaccharide is non-toxic and biodegradable, and it has antiviral and anticoagulant properties (De Araujo et al, 2013;De S.F-Tischer et al, 2006;Jiao et al, 2011;Misurcova, Orsavova, & Ambrozova, 2015;Yermak & Khotimchenko, 2003). A κ-carrageenan macromolecule is composed of repeating carrabiose units which consist of recurrent structures of 3-O-substituted 4-sulfo-β-and 4-O-substituted 3,6-anhydro-α-D-galactopiranose connected by alternating (1-4) and (1-3) glycoside bonds (Fig.…”

Chemical and Spectral Characterization of The Ozonation Products of κ-Carrageenan

“…Large molecular size of κ-carrageenan have limited applications as it is insoluble in water and it forms viscous solution. Converting the High Molecular Weight Fraction of carrageenan (HMWF) into Low Molecular Weight of carrageenan (LMWF) will construct the bioavailability and enlarge the potential uses of carrageenan in pharmaceutical and biomedical [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

“…. It is has been known that depolymerization of polysaccharides by ozonation process leads to some chemical changes such as the formation of carbonyl, carboxyl or double bonds [6,10,15]. In the degradation of chitosan, oxidation of functional groups by hydrogen peroxide give the results of ring-opening reaction, the formation of carboxyl groups and deamination [27].…”