Aqueous RAFT Synthesis of Glycopolymers for Determination of Saccharide Structure and Concentration Effects on Amyloid β Aggregation

Pradipta K. Das, University of Southern Mississippi
Dexter N. Dean, University of Southern Mississippi
April L. Fogel, University of Southern Mississippi
Fei Liu, University of Alabama, Birmingham
Brooks A. Abel, University of Southern Mississippi
Charles L. McCormick, University of Southern Mississippi
Eugenia Karlampieva, University of Alabama, Birmingham
Vijayaraghavan Rangachari, University of Southern Mississippi
Sarah E. Morgan, University of Southern Mississippi


GM1 ganglioside is known to promote amyloid-beta (A beta) peptide aggregation in Alzheimer's disease. The roles of the individual saccharides and their distribution in this process are not understood. Acrylamide-based glycomonomers with either beta-D-glucose or beta-D-galactose pendant groups were synthesized to mimic the stereochemistry of saccharides present in GM1 and characterized via H-1 NMR and electrospray ionization mass spectrometry. Glycopolymers of different molecular weights were synthesized by aqueous reversible addition-fragmentation chain transfer (aRAFT) polymerization and characterized by NMR and GPC. The polymers were used as models to investigate the effects of molecular weight and saccharide unit type on A beta aggregation via thioflavin-T fluorescence and PAGE. High molecular weight (similar to 350 DP) glucose-containing glycopolymers had a profound effect on A beta aggregation, promoting formation of soluble oligomers of A beta and limiting fibril production, while the other glycopolymers and negative control had little effect on the A beta propagation process.