Imperial College London
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Professor Matthew J. Fuchter

Faculty of Natural Sciences, Department of Chemistry

Professor of Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5815m.fuchter

 
 
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Location

 

110DMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lam:2020:10.1021/jacs.0c06811,
author = {Lam, P-Y and Thawani, AR and Balderas, E and White, AJP and Chaudhuri, D and Fuchter, MJ and Peterson, R},
doi = {10.1021/jacs.0c06811},
journal = {Journal of the American Chemical Society},
pages = {17457--17468},
title = {TRPswitch — a step function chemo-optogenetic ligand for the vertebrate TRPA1 channel},
url = {http://dx.doi.org/10.1021/jacs.0c06811},
volume = {142},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Chemo-optogenetics has produced powerful tools for optical control of cell activity, but current tools suffer from a variety of limitations including low unitary conductance, the need to modify the target channel, or the inability to control both on and off switching. Using a zebrafish behavior-based screening strategy, we discovered “TRPswitch”, a photoswitchable non-electrophilic ligand scaffold for the transient receptor potential ankyrin 1 (TRPA1) channel. TRPA1 exhibits high unitary channel conductance, making it an ideal target for chemo-optogenetic tool development. Key molecular determinants for the activity of TRPswitch were elucidated and allowed for replacement of the TRPswitch azobenzene with a next-generation azoheteroarene. The TRPswitch compounds enable reversible, repeatable, and nearly quantitative light-induced activation and deactivation of the vertebrate TRPA1 channel with violet and green light, respectively. The utility of TRPswitch compounds was demonstrated in larval zebrafish hearts exogenously expressing zebrafish Trpa1b, where heartbeat could be controlled using TRPswitch and light. Therefore, TRPA1/TRPswitch represents a novel step-function chemo-optogenetic system with a unique combination of high conductance, high efficiency, activity against an unmodified vertebrate channel, and capacity for bidirectional optical switching. This chemo-optogenetic system will be particularly applicable in systems where a large depolarization current is needed or sustained channel activation is desirable.
AU  - Lam,P-Y
AU  - Thawani,AR
AU  - Balderas,E
AU  - White,AJP
AU  - Chaudhuri,D
AU  - Fuchter,MJ
AU  - Peterson,R
DO  - 10.1021/jacs.0c06811
EP  - 17468
PY  - 2020///
SN  - 0002-7863
SP  - 17457
TI  - TRPswitch — a step function chemo-optogenetic ligand for the vertebrate TRPA1 channel
T2  - Journal of the American Chemical Society
UR  - http://dx.doi.org/10.1021/jacs.0c06811
UR  - https://pubs.acs.org/doi/10.1021/jacs.0c06811
UR  - http://hdl.handle.net/10044/1/82965
VL  - 142
ER  -
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