Aqueous RAFT Synthesis of Glycopolymers for Determination of Saccharide Structure and Concentration Effects on Amyloid β Aggregation
Document Type
Article
Publication Date
9-11-2017
Department
Chemistry and Biochemistry
School
Mathematics and Natural Sciences
Abstract
GM1 ganglioside is known to promote amyloid-β (Aβ) 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 β-d-glucose or β-d-galactose pendant groups were synthesized to mimic the stereochemistry of saccharides present in GM1 and characterized via 1H 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 Aβ aggregation via thioflavin-T fluorescence and PAGE. High molecular weight (∼350 DP) glucose-containing glycopolymers had a profound effect on Aβ aggregation, promoting formation of soluble oligomers of Aβ and limiting fibril production, while the other glycopolymers and negative control had little effect on the Aβ propagation process.
Publication Title
Biomacromolecules
Volume
18
Issue
10
First Page
3359
Last Page
3366
Recommended Citation
Das, P. K.,
Dean, D.,
Fogel, A.,
Liu, F.,
Abel, B.,
McCormick, C. L.,
Kharlampieva, E.,
Rangachari, V.,
Morgan, S. E.
(2017). Aqueous RAFT Synthesis of Glycopolymers for Determination of Saccharide Structure and Concentration Effects on Amyloid β Aggregation. Biomacromolecules, 18(10), 3359-3366.
Available at: https://aquila.usm.edu/fac_pubs/14902