Switchable foldamer ion channels with antibacterial activity

Anna D. Peters; Stefan Borsley; Flavio Della Sala; Dominic F. Cairns-Gibson; Marios Leonidou; Jonathan Clayden; George F.S. Whitehead; Iñigo J. Vitórica-Yrezábal; Eriko Takano; John Burthem; Scott L. Cockroft; Simon J. Webb

doi:10.1039/D0SC02393K

Switchable foldamer ion channels with antibacterial activity

Anna D. Peters, Stefan Borsley, Flavio Della Sala, Dominic F. Cairns-Gibson, Marios Leonidou, Jonathan Clayden, George F.S. Whitehead, Iñigo J. Vitórica-Yrezábal, Eriko Takano, John Burthem, Scott L. Cockroft, Simon J. Webb^*

^*Corresponding author for this work

School of Chemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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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 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 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.

Original language	English
Pages (from-to)	7023-7030
Number of pages	8
Journal	Chemical Science
Volume	11
Issue number	27
DOIs	https://doi.org/10.1039/D0SC02393K
Publication status	Published - 21 Jul 2020

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title = "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 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 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.",

author = "Peters, {Anna D.} and Stefan Borsley and {Della Sala}, Flavio and Cairns-Gibson, {Dominic F.} and Marios Leonidou and Jonathan Clayden and Whitehead, {George F.S.} and Vit{\'o}rica-Yrez{\'a}bal, {I{\~n}igo J.} and Eriko Takano and John Burthem and Cockroft, {Scott L.} and Webb, {Simon J.}",

year = "2020",

month = jul,

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doi = "10.1039/D0SC02393K",

language = "English",

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TY - JOUR

T1 - Switchable foldamer ion channels with antibacterial activity

AU - Peters, Anna D.

AU - Borsley, Stefan

AU - Della Sala, Flavio

AU - Cairns-Gibson, Dominic F.

AU - Leonidou, Marios

AU - Clayden, Jonathan

AU - Whitehead, George F.S.

AU - Vitórica-Yrezábal, Iñigo J.

AU - Takano, Eriko

AU - Burthem, John

AU - Cockroft, Scott L.

AU - Webb, Simon J.

PY - 2020/7/21

Y1 - 2020/7/21

N2 - 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 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.

AB - 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 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.

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U2 - 10.1039/D0SC02393K

DO - 10.1039/D0SC02393K

M3 - Article (Academic Journal)

VL - 11

SP - 7023

EP - 7030

JO - Chemical Science

JF - Chemical Science

SN - 2041-6520

IS - 27

ER -

Switchable foldamer ion channels with antibacterial activity

Abstract

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