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- W2344554114 abstract "γ-AApeptides are a new class of antibacterial peptidomimetics that are not prone to antibiotic resistance and are highly resistant to protease degradation. It is not clear how γ-AApeptides interact with bacterial membranes and alter lipid assembly, but such information is essential to understanding their antimicrobial activities and guiding future design of more potent and specific antimicrobial agents. Using electron paramagnetic resonance techniques, we characterized the membrane interaction and destabilizing mechanism of a lipo-cyclic-γ-AApeptide (AA1), which has broad-spectrum antibacterial activities. The analyses revealed that AA1 binding increases the membrane permeability of POPC/POPG liposomes, which mimic negatively charged bacterial membranes. AA1 binding also inhibits membrane fluidity and reduces solvent accessibility around the lipid headgroup region. Moreover, AA1 interacts strongly with POPC/POPG liposomes, inducing significant lipid lateral-ordering and membrane thinning. In contrast, minimal membrane property changes were observed upon AA1 binding for liposomes mimicking mammalian cell membranes, which consist of neutral lipids and cholesterol. Our findings suggest that AA1 interacts and disrupts bacterial membranes through a carpet-like mechanism. The results showed that the intrinsic features of γ-AApeptides are important for their ability to disrupt bacterial membranes selectively, the implications of which extend to developing new antibacterial biomaterials." @default.
- W2344554114 created "2016-06-24" @default.
- W2344554114 creator A5034454888 @default.
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- W2344554114 creator A5054341281 @default.
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- W2344554114 date "2016-04-01" @default.
- W2344554114 modified "2023-10-16" @default.
- W2344554114 title "Selective Membrane Disruption Mechanism of an Antibacterial γ-AApeptide Defined by EPR Spectroscopy" @default.
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- W2344554114 doi "https://doi.org/10.1016/j.bpj.2016.02.038" @default.
- W2344554114 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4850324" @default.
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- W2344554114 hasPublicationYear "2016" @default.
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