Multivalent glycoconjugates as vaccines and potential drug candidates

Abstract

Pathogens adhere to the host cells during the first steps of infection through multivalent interactions which involve protein-glycan recognition. Multivalent interactions are also involved at different stages of immune response. Insights into these multivalent interactions generate a way to use suitable carbohydrate ligands that are attached to a basic scaffold consisting of e.g., dendrimer, polymer, nanoparticle, etc., with a suitable linker. Thus a multivalent architecture can be obtained with controllable spatial and topology parameters which can interfere with pathogen adhesion. Multivalent glycoconjugates bearing natural or unnatural carbohydrate antigen epitopes have also been used as carbohydrate based vaccines to stimulate an innate and adaptive immune response. Designing and synthesizing an efficient multivalent architecture with optimal ligand density and a suitable linker is a challenging task. This review presents a concise report on the endeavors to potentially use multi-and polyvalent glycoconjugates as vaccines as well as anti-infectious and anti-inflammatory drug candidates.

Not Just for Tumor Targeting: Unmet Medical Needs and Opportunities for Nanomedicine

“…For instance, Prevnar13 ® , a tridecavalent glycoconjugate of 13 carbohydrate antigens linked to a diphtheria carrier protein, has recently been approved as synthetic pneumococcal vaccine in the clinics [42]. Similarly multivalent glycoantigen presentation to B cells can also successfully be provided by various types of nanoparticles to enhance humoral immune response toward infectious diseases [43].…”

Fullerenes in biology and medicine

“…5 Since then, efficient synthetic methods for fullerene functionalization have been developed. 6, 7 Functionalization with bioactive compounds that exhibit affinity to certain nucleic acids, proteins or cell receptors such as peptides 8-10 or saccharides, 11, 12 functionalization with polar or ionic groups such as hydroxyl, 13, 14 carbonyl 15-17 or quaternary ammonium salts, 18, 19 and encapsulation with macromolecules 20, 21 are the most common approaches to synthesize water-soluble fullerene derivatives for biomedical applications. 22-26 …”

Multivalent Interactions of Polyamide Based Sequence‐Controlled Glycomacromolecules with Concanavalin A

“…Given the low affinity of protein–carbohydrate interactions, it is important to design multivalent carbohydrates exhibiting biologically relevant interaction to protein receptors. Researchers have established various types of scaffolds presenting sugars for high‐affinity binding, for example, 2D surfaces, microgels, nanoparticles, hydrogel beads, dendrimers, or polymers . Due to the low affinity and comparatively short lifetime of single carbohydrate–protein complexes, carbohydrates presented on polymeric scaffolds (glycopolymers) predominantly show an additive, “statistical” contribution when binding to receptors .…”