Multi-step strategies for the regioselective sulfation of polysaccharides from eco-sustainable sources

Polysaccharides are the most abundant biomacromolecules on our planet, possessing enormous structural diversity and functional versatility. An important group of natural polysaccharides comprises the sulfated ones, which perform key biological functions. The most important animal sourced sulfated polysaccharides are glycosaminoglycans (GAGs), which are found in the extracellular matrix of animal cells. Some of them are exploited in already approved therapeutic treatments, and a significant number of novel drugs are currently under development.1 Nonetheless, naturally occurring GAGs exhibit variable chemical compositions and biological activities, which could cause unpredictable results during applications. However, sulfated polysaccharides can also be obtained in a semi-synthetic way: the introduction of sulfate groups into the backbones of natural unsulfated polysaccharides, allows to endow them with bioactivities similar to sulfated GAGs but without risks derived from their typical animal sources.2 In this frame, a special interest is focused on the sulfation of polysaccharides from eco-sustainable natural and/or biotech sources (algae, fungi, plants, bacteria). In particular, the attention is focused on polysaccharides already used in the biomedical and/or food fields, to improve their biological properties or to introduce new ones through chemical modifications. Regioselective sulfation reactions can be conducted through multi-step strategies consisting in protection-sulfation-deprotection sequences.3 The polysaccharides selected to this aim are alginate, a copolymer of 1→4-linked -D-mannuronic acid (M) and -L-guluronic acid (G), curdlan4, a -1→3-glucan produced, for commercial purposes, from mutant Agrobacterium strains, and finally an exopolysaccharides (EPSs)5 from Vibrio diabolicus HE800 strain, a polysaccharide highly resembling GAGs structure due to the presence, in its backbone, of aminosugars and uronic acids. The final goal is to obtain new polysaccharide-based products for biomedical application, which can be proposed as substitutes for drugs already existing but obtained from less eco-sustainable sources.