Boles, Jessica E., Bennett, Charlotte, Baker, Jennifer, Hilton, Kira L. F., Kotak, Hiral A. ORCID: https://orcid.org/0000-0002-1080-3494, Clark, Ewan R. ORCID: https://orcid.org/0000-0001-7287-2631, Long, Yifan, White, Lisa J., Lai, Hin Yuk, Hind, Charlotte K., Sutton, J. Mark, Garrett, Michelle D., Cheasty, Anne, Ortega-Roldan, Jose L. ORCID: https://orcid.org/0000-0002-6316-4390, Charles, Mark, Haynes, Cally J. E. ORCID: https://orcid.org/0000-0003-4262-8560 and Hiscock, Jennifer R. ORCID: https://orcid.org/0000-0002-1406-8802 (2022) Establishing the selective phospholipid membrane coordination, permeation and lysis properties for a series of ‘druggable’ supramolecular self-associating antimicrobial amphiphiles. Chemical Science, 13 (33). pp. 9761-9773. ISSN 2041-6520 (Print), 2041-6539 (Online) (doi:10.1039/D2SC02630A)

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Abstract

The rise of antimicrobial resistance remains one of the greatest global health threats facing humanity. Furthermore, the development of novel antibiotics has all but ground to a halt due to a collision of intersectional pressures. Herein we determine the antimicrobial efficacy for 14 structurally related supramolecular self-associating amphiphiles against clinically relevant Gram-positive methicillin resistant Staphylococcus aureus and Gram-negative Escherichia coli . We establish the ability of these agents to selectively target phospholipid membranes of differing compositions, through a combination of computational host:guest complex formation simulations, synthetic vesicle lysis, adhesion and membrane fluidity experiments, alongside our novel 1 H NMR CPMG nanodisc coordination assays, to verify a potential mode of action for this class of compounds and enable the production of evermore effective next-generation antimicrobial agents. Finally, we select a 7-compound subset, showing two lead compounds to exhibit ‘druggable’ profiles through completion of a variety of in vivo and in vitro DMPK studies.

Item Type:	Article
Additional Information:	All publication charges for this article have been paid for by the Royal Society of Chemistry.
Uncontrolled Keywords:	supramolecular, membrane, antimicrobial
Subjects:	Q Science > Q Science (General) Q Science > QR Microbiology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	02 Apr 2026 15:10
URI:	https://gala.gre.ac.uk/id/eprint/52713

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