S. Laroque, M. Reifarth, M. Sperling, S. Kersting, S. Klöpzig, P. Budach, J. Storsberg, M. Hartlieb
Impact of Multivalence and Self-Assembly in the Design of Polymeric Antimicrobial Peptide Mimics
ACS Appl. Mater. Interfaces 2020, 12, 30052-30065
DOI: 10.1021/acsami.0c05944
Antimicrobial resistance is an increasingly serious challenge for public health and could result in dramatic negative consequences for the health care sector during the next decades. In order to solve this problem, antibacterial materials which are unsusceptible towards the development of bacterial resistance are a promising branch of research. Within this work, a new type of polymeric antimicrobial peptide mimic featuring a bottle brush architecture is developed, using a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and ring-opening metathesis polymerization (ROMP). This approach enables multivalent presentation of antimicrobial subunits resulting in improved bioactivity and an increased hemocompatibility, boosting the selectivity of these materials for bacterial cells. Direct probing of membrane integrity of treated bacteria revealed a highly potent membrane disruption caused by bottle brush copolymers. Multivalent bottle brush copolymers clearly out-performed their linear equivalents regarding bioactivity and selectivity.The effect of segmentation of cationic and hydrophobic sub-units within bottle brushes was probed using hetero graft-copolymers. These materials were found to self-assemble under physiological conditions, which reduced their antibacterial activity, highlighting the importance of precise structural control for such applications.To the best of our knowledge this is the first example to demonstrate the positive impact of multivalence, generated by a bottle brush topology in polymeric antimicrobial peptide mimics, making these polymers a highly promising material platform for the design of new bactericidal systems.
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