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

作者：Das, Pradipta K.; Dean, Dexter N.; Fogel, April L.; Liu, Fei; Abel, Brooks A.; McCormick, Charles L.; Kharlampieva, Eugenia; Rangachari, Vijayaraghavan; Morgan, Sarah E.^*

来源：Biomacromolecules, 2017, 18(10): 3359-3366.

DOI：10.1021/acs.biomac.7b01007

• MACROCYCLIC GLYCOCLUSTERS
• POLYMERIZATION
• PROTEIN
• INHIBITION
• POLYMERS
• GLYCOSAMINOGLYCANS
• GANGLIOSIDES
• FLUORESCENCE
• ASSOCIATION
• AMPHIPHILES

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.

• 出版日期2017-10