Glycosaminoglycan model polymers with Poly(γ-glutamate) backbone to inhibit aggregation of β-Amyloid peptide

Biocompatible glycosaminoglycans (GAG)-mimicking polymers containing both sulfate and carboxyl groups were synthesized by combining poly(λ- glutamate) (PGA) with sulfonates. GAG-mimicking polymers were synthesized by introducing the sulfate compounds 6S-GlcNAc and taurine into PGA. The inhibitory activities of the GAG-mimicking glycopolymers for Aβ (1-40) aggregation were evaluated from the fluorescent ratio changes with the thioflavin-T (th-T) assay. The time-course of the fluorescence changes without additives showed a gradual increase for 24 h of incubation, indicating aggregation of Aβ, and the lag time before a steep increase in fluorescence was around 6 h. Circular dichroism spectroscopy of Aβ with/without GAG mimicking glycopolymers was also performed. The band intensity around 218nm of Aβ with a GAG mimicking polymer was smaller than that without additives, and suggested a decrease the β-sheet structure, based on interactions between Aβ (1-40) and the GAG-mimicking glycopolymer.