Alzheimer's disease (AD) is a growing problem worldwide, making research on AD pathogenesis a pressing need. Currently, a great deal of research is focused on the specific impact of amyloid � (A�) peptides on AD etiology, as these peptides represent a major component of the fibril plaques that are characteristic of AD. Through interaction with various modulators, such as phosphatidylserine and GM1 ganglioside, A� peptides have been shown to undergo conformational change and aggregate into toxic species. Until recently, fibrils were thought to be the predominant toxic species; however, current research indicates that oligomers might be the more toxic of the two, as a discrepancy exists between the observed severity of AD and the presence of fibrils. The goal of this research, therefore, is to create synthetic polymer models with substituent groups that mimic the saccharide head group of gangliosides and the anionic phosphate moiety of phosphatidylserine, through the use of RAFT polymerization, in order investigation the predominance of either oligomers or fibrils in the presence of each modulator. To accomplish this, a series of homopolymers and statistical copolymers, derived from monomers 2-(b-D-glucosyloxy)ethyl acrylamide [GlcEAm], 2-(b-D-galactosyloxy)ethyl acrylamide [GalEAm] and 2-acrylamidoethyl dihydrogen phosphate [AEDP], were synthesized. The polymers were characterized through 1H NMR, and ASEC-MALLS. Conformational changes and aggregation were analyzed through thioflavin (ThT) fluorescence, circular dichroism (CD), polyacrylamide gel electrophoresis (PAGE), and atomic force microscopy (AFM).

Synthesis of polysaccharide and phospholipid mimics for determination of amyloid-� peptide aggregation as a function of cellular composition

247th National Meeting (2014)

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