Syntheses and functions of Glycosaminoglycan mimicking polymers

Abstract

Glycosaminoglycans (GAGs) are important polysaccharides in the living system. Though total syntheses of GAGs oligosaccharides have been reported, it is still difficult to obtain GAGs. In this investigation, GAGs mimetics were prepared by polymerization of vinyl sugars instead of total synthesis. Glycopolymers are polymers with pendant saccharides, and exhibit a strong molecular recognition due to the multivalency. GAGs mimicking glycopolymers were prepared by polymerizing acrylamide derivatives carrying sulfated N-acetyl glucosamine (GlcNAc). The polymer interactions with proteins were investigated. The glycopolymer libraries were prepared with varying molecular weight, sugar structure, and sugar ratios. The GAG glycopolymers with biodegradable backbone, dendrimer, and arrays were also prepared. The inhibitory activity of Alzheimer amyloid beta peptides by the glycopolymers was investigated in detail. The glycopolymer with sulfated GlcNAc inhibited the aggregation of amyloid beta (Aβ) and the multivalency of sulfated GlcNAc was the key of the interaction. The activity depends on the chemical structure of glycopolymers. Also, the sulfated saccharide function was correlated to the functions of native GAGs.