Synthesis of Fucoidan-Biomimetic Glycopolymers with Flexible Skeletons for Enhanced Anti-Herpes Virus Efficacy.

Abstract

Synthetic glycopolymers can be designed to mimic the structure and biological function of natural polysaccharides, offering a wide range of potential applications in the pharmaceutical and medicine. Nevertheless, amphiphilic synthetic glycopolymers commonly form biologically inert nanomicelle structures in aqueous solutions through spontaneous self-assembly. Envisioning that preventing self-assembly is pivotal to the full realization of the biological activities of the glycopolymers, we design and prepare a class of norbornene-derived hydrophilic glycopolymers containing sulfated fucose amenable to skeleton modification through ring-opening metathesis polymerization (ROMP). The skeleton of the fucoidan glycopolymers was chemically modified with hydrogen reduction, dihydroxylation, and oxidation following subsequent sulfation. We conducted physicochemical property characterization of the skeleton-modified glycopolymers to demonstrate that the hydrophilic glycopolymers have a more flexible structure compared to conventional polymers, and the sulfated fucoidan glycopolymers form a non-assembly morphology similar to the natural polysaccharides. Furthermore, the non-assembly glycopolymers exhibit significantly enhanced anti-HSV-1 activities. Our findings underscore the significance of the rational design of polymer skeletons in the development of structural and functional mimics of natural polysaccharides.