Synthetic Glycans and Glycomimetics: A Promising Alternative to Natural Polysaccharides

Abstract

A large quantity of polysaccharide-derived conjugate vaccines have been developed to combat various pathogenic infections. Another prominent polysaccharide, heparin, is listed as an essential drug by the World Health Organization (WHO) to treat thrombus. One of their common problems is that they all derive from natural polysaccharides. Specifically, capsular polysaccharides are mainly obtained from bacterial fermentation and unfractionated heparin is extracted from animal tissues such as porcine mucosa. The quality of natural polysaccharides is inconsistent and traces of contamination would cause a disaster. By contrast, the use of chemical or chemoenzymatic methods could provide structurally homogeneous and quality-controlled glycans. To date, large numbers of polysaccharide fragments and their analogues have been synthesized and evaluated. Some of them even showed comparable activities to their corresponding natural polysaccharides. Here, the latest advances in these synthetic glycan analogues ranging from carbohydrate-based vaccines, heparin-related therapeutics and glycomimetics of polysaccharides are summarized.

Diabetic endothelial colony forming cells have the potential for restoration with glycomimetics

“…The glycocalyx is composed of glycosaminoglycans (GAGs), which are major components of the extracellular matrix (ECM) and exist as a diverse array of differentially sulfated disaccharide units 17,18 . An important GAG for angiogenesis and wound healing is Heparan Sulfate (HS), and due to its varying sulfation patterning, creates an opportunity to generate smaller, functional HS mimics 19,20 . Glycomimetics can act as regulatory molecules, with targeted therapeutic potential 16 ; however, their exploitation has been hindered by the complexity of their synthesis.…”

A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A

“…Strategies for the chemical or enzymatic synthesis of natural MenA structures have been proposed 25,26 . Differently from these approaches, we envisaged the use of synthetic chemistry to generate stabilized MenA glycomimetics 27,28 . Mimics, in which structural changes are implemented to improve specific features of the natural polysaccharide have so far not been incorporated in conjugate vaccines inducing protective immune responses 29 .…”

Advances in Targeting HPV Infection as Potential Alternative Prophylactic Means

“…Most recently, the potential of highly sulfated glycomimetics as inhibitors of HPV binding and infection has been assessed [ 116 ]. Glycomimetics are synthetic glycan analogues which can even exceed the activities of the natural polysaccharides from which they are derived [ 117 ]. These synthetic analogues have enhanced stability, bioavailability, and half-life, making them ideal molecules to explore in their capacity as antivirals.…”