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. To solve this problem, antibacterial materials that are unsusceptible toward the development of bacterial resistance are a promising branch of research. In this work, a new type of polymeric antimicrobial peptide mimic featuring a bottlebrush 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 highly potent membrane disruption caused by bottlebrush copolymers. Multivalent bottlebrush copolymers clearly outperformed their linear equivalents regarding bioactivity and selectivity. The effect of segmentation of cationic and hydrophobic subunits within bottle brushes was probed using heterograft 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 bottlebrush topology in polymeric antimicrobial peptide mimics, making these polymers a highly promising material platform for the design of new bactericidal systems.

中文翻译：

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多价和自组装对聚合物抗菌肽模拟物设计的影响。

抗菌素耐药性是对公共卫生日益严峻的挑战，并可能在未来几十年内对卫生保健部门造成巨大的负面影响。为了解决这个问题，对细菌抗性的发展不敏感的抗菌材料是有前途的研究领域。在这项工作中，结合可逆加成-断裂链转移（RAFT）聚合和开环易位聚合（ROMP）的组合，开发了一种新型的具有瓶刷结构的聚合物抗菌肽模拟物。这种方法能够实现抗菌亚基的多价呈递，从而提高了生物活性，并增加了血液相容性，从而提高了这些材料对细菌细胞的选择性。直接探查处理过的细菌的膜完整性发现了由洗瓶刷共聚物引起的强力膜破坏。就生物活性和选择性而言，多价洗瓶刷共聚物明显优于其线性当量。使用异质接枝共聚物探讨了瓶刷中阳离子和疏水亚基的分割效果。发现这些材料在生理条件下会自组装，这降低了它们的抗菌活性，突出了此类应用中精确结构控制的重要性。据我们所知，这是第一个证明多价对聚合物抗菌肽模拟物产生的牙刷拓扑结构产生积极影响的例子，