Date of Award

Spring 5-8-2015

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Polymers and High Performance Materials

Committee Chair

Sarah E. Morgan

Committee Chair Department

Polymers and High Performance Materials

Committee Member 2

Charles McCormick

Committee Member 2 Department

Polymers and High Performance Materials

Committee Member 3

Daniel Savin

Committee Member 3 Department

Polymers and High Performance Materials

Committee Member 4

Derek Patton

Committee Member 4 Department

Polymers and High Performance Materials

Committee Member 5

Vijay Rangachari

Committee Member 5 Department

Chemistry and Biochemistry

Abstract

The first section of this work describes the synthesis and characterization of novel glycopolymers synthesized to model GM1 gangliosides, a glycolipid found in neuronal cells. Glucose and galactose were attached to N-hydroxyethyl acrylamide, using chemistry that granted control over the stereochemistry at the C1’ carbon of each saccharide, and polymerized via aqueous RAFT (aRAFT). Homopolymers, targeting either 30 or 300 DP, and copolymers, with N-dimethyl acrylamide, were prepared as a glycopolymer platform for investigation of amyloid β (Aβ), a naturally occurring peptide associated with Alzheimer’s disease, aggregation. Aβ aggregation kinetics and aggregate size in the presence of glycopolymer were determined.

The second section of this work describes N-(3-guanadinopropyl)methacrylamide (GPMA) synthesis, homopolymerization and copolymerization with N-(3-aminopropyl) methacrylamide (APMA) using aRAFT. Many naturally occurring AMPs have an abundance of lysine and arginine. GPMA, an arginine mimic, was incorporated into our established acrylamide based antimicrobial peptide (AMP) platform with APMA, a lysine mimic, to increase the activity and selectivity of our AMPs over a wider range of bacteria. Antimicrobial activity, against E. coli, S. aureus, and P. aeruginosa, and selectivity, against human red blood cells and cancer cells, was determined for the GPMA and APMA homopolymers and copolymers. The effect of GPMA counterion on activity and selectivity was also investigated.

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