Design, synthesis, and biomedical applications of synthetic sulphated polysaccharides

Sulphated polysaccharides play important roles in a number of physiological and patho-physiological processes including the coagulation cascade, viral transmission, and antioxidation. In nature, sulphated polysaccharides are highly diverse, possessing variations in the carbohydrate backbone, location of the sulphate group(s), and degree of sulphation. These compositional attributes lead to varied sulphated polymers with different negative charge densities and resultant structure-property-activity relationships. Sulphating naturally occurring polysaccharides and their synthetic analogs is challenging, and traditionally requires harsh conditions and long reaction times, often causing non-selective sulphation at different and/or multiple hydroxyl positions. In this Review, we begin with a discussion of both established and novel methods and reagents for sulphation of these polymers, along with the advantages and disadvantages of these various approaches. Next, we describe characterization methods to confirm sulphation. Finally, we provide examples of synthetically sulphated natural polysaccharides and sulphated synthetic polysaccharides, and discuss the utility of these novel polymers in various biomedical applications. This review provides a comprehensive analysis of synthetic sulphated polysaccharides, their current uses, and highlights biomedical opportunities. This review summarizes the synthetic methods to sulphated polysaccharides, describes their compositional and structural diversity in regards to activity, and showcases their biomedical applications.