Controlling transmembrane ion transport via photo-regulated carrier mobility

Stimuli-responsive transmembrane ion carriers allow for targeted and controllable transport activity, with potential applications as therapeutics for channelopathies and cancer, and in fundamental studies into ion transport phenomena. These applications require OFF–ON activation from a fully inactiv...

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Những tác giả chính: Bickerton, L, Langton, MJ
Định dạng: Journal article
Ngôn ngữ:English
Được phát hành: Royal Society of Chemistry 2022
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author Bickerton, L
Langton, MJ
author_facet Bickerton, L
Langton, MJ
author_sort Bickerton, L
collection OXFORD
description Stimuli-responsive transmembrane ion carriers allow for targeted and controllable transport activity, with potential applications as therapeutics for channelopathies and cancer, and in fundamental studies into ion transport phenomena. These applications require OFF–ON activation from a fully inactive state which does not exhibit background activity, but this remains challenging to achieve with synthetic transport systems. Here we introduce a novel mechanism for photo-gating mobile ion carriers, which involves modulating the mobility of the carriers within the lipid bilayer membrane. By appending a membrane-targeting anchor to the carrier using a photo-cleavable linker, the carrier's ion transport activity is fully switched off by suppressing its ability to shuttle between the two aqueous-membrane interfaces of the bilayer. The system can be reactivated rapidly in situ within the membrane by photo-triggered cleavage of the anchor to release the mobile ion carrier. This approach does not involve direct functionalization of the ion binding site of the carrier, and so does not require the de novo design of novel ion binding motifs to implement the photo-caging of activity. This work demonstrates that controlling the mobility of artificial transport systems enables precise control over activity, opening up new avenues for spatio-temporally targeted ionophores.
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spelling oxford-uuid:7ac953b1-6b0c-4e6b-8959-0dbeb6f4a5d32023-02-10T12:16:10ZControlling transmembrane ion transport via photo-regulated carrier mobilityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7ac953b1-6b0c-4e6b-8959-0dbeb6f4a5d3EnglishSymplectic ElementsRoyal Society of Chemistry2022Bickerton, LLangton, MJStimuli-responsive transmembrane ion carriers allow for targeted and controllable transport activity, with potential applications as therapeutics for channelopathies and cancer, and in fundamental studies into ion transport phenomena. These applications require OFF–ON activation from a fully inactive state which does not exhibit background activity, but this remains challenging to achieve with synthetic transport systems. Here we introduce a novel mechanism for photo-gating mobile ion carriers, which involves modulating the mobility of the carriers within the lipid bilayer membrane. By appending a membrane-targeting anchor to the carrier using a photo-cleavable linker, the carrier's ion transport activity is fully switched off by suppressing its ability to shuttle between the two aqueous-membrane interfaces of the bilayer. The system can be reactivated rapidly in situ within the membrane by photo-triggered cleavage of the anchor to release the mobile ion carrier. This approach does not involve direct functionalization of the ion binding site of the carrier, and so does not require the de novo design of novel ion binding motifs to implement the photo-caging of activity. This work demonstrates that controlling the mobility of artificial transport systems enables precise control over activity, opening up new avenues for spatio-temporally targeted ionophores.
spellingShingle Bickerton, L
Langton, MJ
Controlling transmembrane ion transport via photo-regulated carrier mobility
title Controlling transmembrane ion transport via photo-regulated carrier mobility
title_full Controlling transmembrane ion transport via photo-regulated carrier mobility
title_fullStr Controlling transmembrane ion transport via photo-regulated carrier mobility
title_full_unstemmed Controlling transmembrane ion transport via photo-regulated carrier mobility
title_short Controlling transmembrane ion transport via photo-regulated carrier mobility
title_sort controlling transmembrane ion transport via photo regulated carrier mobility
work_keys_str_mv AT bickertonl controllingtransmembraneiontransportviaphotoregulatedcarriermobility
AT langtonmj controllingtransmembraneiontransportviaphotoregulatedcarriermobility