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Switchable foldamer ion channels with antibacterial activity.

ABSTRACT: Synthetic ion channels may have applications in treating channelopathies and as new classes of antibiotics, particularly if ion flow through the channels can be controlled. Here we describe triazole-capped octameric ?-aminoisobutyric acid (Aib) foldamers that "switch on" ion channel activity in phospholipid bilayers upon copper(ii) chloride addition; activity is "switched off" upon copper(ii) extraction. X-ray crystallography showed that CuCl2 complexation gave chloro-bridged foldamer dimers, with hydrogen bonds between dimers producing channels within the crystal structure. These interactions suggest a pathway for foldamer self-assembly into membrane ion channels. The copper(ii)-foldamer complexes showed antibacterial activity against B. megaterium strain DSM319 that was similar to the peptaibol antibiotic alamethicin, but with 90% lower hemolytic activity.

SUBMITTER: Peters AD

PROVIDER: S-EPMC7481839 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Switchable foldamer ion channels with antibacterial activity.

Peters Anna D AD Borsley Stefan S Della Sala Flavio F Cairns-Gibson Dominic F DF Leonidou Marios M Clayden Jonathan J Whitehead George F S GFS Vitórica-Yrezábal Iñigo J IJ Takano Eriko E Burthem John J Cockroft Scott L SL Webb Simon J SJ

Chemical science 20200604 27

Synthetic ion channels may have applications in treating channelopathies and as new classes of antibiotics, particularly if ion flow through the channels can be controlled. Here we describe triazole-capped octameric α-aminoisobutyric acid (Aib) foldamers that "switch on" ion channel activity in phospholipid bilayers upon copper(ii) chloride addition; activity is "switched off" upon copper(ii) extraction. X-ray crystallography showed that CuCl<sub>2</sub> complexation gave chloro-bridged foldamer ...[more]

PMID: 32953034

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