Semi-synthesis of glycosaminoglycan-mimetics from bacterial sources for biomedical applications

Sulfated polysaccharides are widely distributed in nature, especially in animal species, and play a key role in several biological processes. 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 therapeutic treatments, and a significant number of novel drugs based on GAGs are currently under development. Nonetheless, naturally occurring GAGs exhibit variable chemical compositions and biological activities, which could cause unpredictable results during applications. Sulfated polysaccharides can also be obtained in a semi-synthetic way: the introduction of sulfate groups into the backbones of natural polysaccharides derived from plant, algae or microbial sources, allows to endow them with bioactivities similar to sulfated GAGs but without risks derived from their typical animal sources. In this frame, a special interest is focused on the regioselective sulfation of polysaccharides already displaying a GAG-like structure in their native form. Regioselective sulfation reactions can be conducted through multi-step strategies consisting in protection-sulfation-deprotection sequences. The exopolysaccharide (EPS) produced by the bacterium Vibrio diabolicus HE800 strain, firstly isolated from the polychaete annelid Alvinella pompejana, is known to have a GAG-like structure. Its modification through multi-step strategies has been performed to obtain new derivatives acting as GAG mimics.