Graduation Year
2022
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Chemistry
Major Professor
Jianfeng Cai, Ph.D.
Committee Member
Kirpal Bisht, Ph.D.
Committee Member
Wenqi Liu, Ph.D.
Committee Member
Feng Cheng, Ph.D.
Keywords
Antibiotic-Resistant, Biofilm Inhibition, Broad-Spectrum Activity, Host-Defense Peptides, Narrow-Spectrum Activity
Abstract
Antimicrobial resistance is a global challenge owing to the lack of discovering effective antibiotic agents. Antimicrobial polymers containing the cationic groups and hydrophobic groups which mimic natural host-defense peptides (HDPs) show great promise in combating bacteria. Herein, we report the synthesis of lipidated polycarbonates bearing primary amino groups and hydrophobic moieties (including both the terminal lipid alkyl chain and hydrophobic groups in the sequences) by ring-opening polymerization. The hydrophobic/hydrophilic group ratios were adjusted deliberately and the lengths of the lipid tails at the end of the polymers were modified to achieve the optimized combination for the lead polymers, which exhibited potent and broad-spectrum bactericidal activity against a panel of Gram-positive and Gram-negative bacteria.
In order to improve biocompatibility while maintaining activity, lysine side chain was introduced to the polycarbonates. By adjusting the length of the lipid tail, broad-spectrum activity as well as low hemolytic lead polymers were found. The lead polymer didn’t significantly affect the cell viability under test conditions.
Comprehensive analyses using biochemical and biophysical assays revealed the strong interaction between the polymers and bacteria membranes. Moreover, the polymers also showed strong biofilm inhibition activity and did not readily induce antibiotic resistance. Our results suggest that lipidated polycarbonates could be a new class of antimicrobial agents.
Meanwhile, the hydrophobic amino acid side chains were also generated. After screening the proper length of lipid tail, this set of polycarbonates could be strain-specific antimicrobial agents when higher amounts of monomer were used together with shorter lipid tails.
Scholar Commons Citation
Gao, Ruixuan, "Development of Lipidated Antimicrobial Polycarbonates" (2022). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10386
