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- W2293009846 abstract "Antibiotic resistance has become one of the greatest challenges in treating bacterial infections in healthcare. Inspired by the structures of bacteria-invading viruses and antimicrobial peptides (AMPs), we hypothesize that in addition to a balance of amphiphilicity and electropositivity, nanostructure is another important structural determinant that defines how membrane-active antibiotics remodel host membranes to gain desirable activity and selectivity. Here we study the structure-activity relationship of a series of polymer molecular brushes (PMBs) with well-defined nanostructures that mimic spherical and rod-shaped viruses. Our preliminary data based on PMBs with hydrophilic polymer brushes reveal that: (1) amphiphilicity is not a required trait - hydrophilic PMBs can be designed to have potent antibiotic performance as well with negligible hemolytic activity; (2) the nanoscale architecture of PMBs defines their double selectivity, not molecular weight per se; (3) PMBs are far more powerful antibiotics than individual linear-chain polymers that make up the PMBs; and (4) nanostructured PMBs induce topological changes of membranes by forming membrane pores that unlikely fit in with any known models of AMP action. These findings expand existing wisdom on designing synthetic mimics of AMPs and suggest that the spatially-defined, multivalent interactions inherent to nanostructured PMBs is of great significance for the development of new membrane-active antibiotics." @default.
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- W2293009846 date "2016-02-01" @default.
- W2293009846 modified "2023-09-26" @default.
- W2293009846 title "Nanostructure-Dependent Antimicrobiotic Activity and Selectivity of Synthetic Membrane-Active Polymers" @default.
- W2293009846 doi "https://doi.org/10.1016/j.bpj.2015.11.487" @default.
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