Naturally occurring antimicrobial peptides (AMPs) are amphipathic molecules that selectively eliminate a wide range of bacteria. The hydrophilic regions of AMPs possess an abundance of lysine and arginine amino acid residues, which are protonated and positively charged under physiological conditions. The positively charged AMPs electrostatically bind with the negatively charged bacterial cell membrane and promote cell death. However, literature on AMP mimics has shown a variation in the mechanism of cell death (e.g. membrane disrupting and cell penetrating), depending on the presence of lysine and arginine, respectively. The goal of this research is to determine the predominant mode of antimicrobial activity for statistical copolymer AMP mimics prepared via aqueous RAFT polymerization. The synthesized statistical copolymers are comprised of varying ratios of aminopropyl methacrylamide (APMA), a lysine mimic, and guanadinopropyl methacrylamide (GPMA), an arginine mimic. The prevailing mechanism of cell death was characterized by dye leakage studies with large unilamellar vesicles (LUVs), containing the fluorescent dye calcein, and then directly correlated to the compositional differences of the copolymers. The statistical copolymer AMP mimics utilized have demonstrated well-defined molar ratios of APMA and GPMA, antimicrobial activity, and biocompatibility. Developing a greater understanding of the structure-activity relationship of synthetic AMPs will aid in the future design of systems tailored to target specific bacterial species.

Synthesis of guanidinium-modified antimicrobial peptide mimics prepared via aqueous RAFT polymerization

247th National Meeting (2014)

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