Effects of Stereochemistry and Hydrogen Bonding on Glycopolymer-Amyloid-β Interactions.

Saccharide stereochemistry plays an important role in carbohydrate functions such as biological recognition processes and protein binding. Synthetic glycopolymers with pendant saccharides of controlled stereochemistry provide an attractive approach for the design of polysaccharide-inspired biomaterials. Acrylamide-based polymers containing either β,d-glucose or β,d-galactose pendant groups, designed to mimic GM1 ganglioside saccharides, and their small-molecule analogues were used to evaluate the effect of stereochemistry on glycopolymer solution aggregation processes alone and in the presence of Aβ42 peptide using dynamic light scattering, gel permeation chromatography-multiangle laser light scattering, and fluorescence assays. Fourier transform infrared and nuclear magnetic resonance (NMR) were employed to determine hydrogen bonding patterns of the systems. The galactose-containing polymer displayed significant intramolecular hydrogen bonding and self-aggregation and minimal association with Aβ42, while the glucose-containing glycopolymers showed intermolecular interactions with the surrounding environment and association with Aβ42. Saturation transfer difference NMR spectroscopy demonstrated different binding affinities for the two glycopolymers to Aβ42 peptide.