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Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement

[Image: see text] Electrochemical biosensors allow the rapid, selective, and sensitive transduction of critical biological parameters into measurable signals. However, current electrochemical biosensors often fail to selectively and sensitively detect small molecules because of their small size and...

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Detalles Bibliográficos
Autores principales: Murugappan, Krishnan, Sundaramoorthy, Uthayasuriya, Damry, Adam M., Nisbet, David R., Jackson, Colin J., Tricoli, Antonio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709943/
https://www.ncbi.nlm.nih.gov/pubmed/36465535
http://dx.doi.org/10.1021/jacsau.2c00291
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author Murugappan, Krishnan
Sundaramoorthy, Uthayasuriya
Damry, Adam M.
Nisbet, David R.
Jackson, Colin J.
Tricoli, Antonio
author_facet Murugappan, Krishnan
Sundaramoorthy, Uthayasuriya
Damry, Adam M.
Nisbet, David R.
Jackson, Colin J.
Tricoli, Antonio
author_sort Murugappan, Krishnan
collection PubMed
description [Image: see text] Electrochemical biosensors allow the rapid, selective, and sensitive transduction of critical biological parameters into measurable signals. However, current electrochemical biosensors often fail to selectively and sensitively detect small molecules because of their small size and low molecular complexity. We have developed an electrochemical biosensing platform that harnesses the analyte-dependent conformational change of highly selective solute-binding proteins to amplify the redox signal generated by analyte binding. Using this platform, we constructed and characterized two biosensors that can sense leucine and glycine, respectively. We show that these biosensors can selectively and sensitively detect their targets over a wide range of concentrations—up to 7 orders of magnitude—and that the selectivity of these sensors can be readily altered by switching the bioreceptor’s binding domain. Our work represents a new paradigm for the design of a family of modular electrochemical biosensors, where access to electrode surfaces can be controlled by protein conformational changes.
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spelling pubmed-97099432022-12-01 Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement Murugappan, Krishnan Sundaramoorthy, Uthayasuriya Damry, Adam M. Nisbet, David R. Jackson, Colin J. Tricoli, Antonio JACS Au [Image: see text] Electrochemical biosensors allow the rapid, selective, and sensitive transduction of critical biological parameters into measurable signals. However, current electrochemical biosensors often fail to selectively and sensitively detect small molecules because of their small size and low molecular complexity. We have developed an electrochemical biosensing platform that harnesses the analyte-dependent conformational change of highly selective solute-binding proteins to amplify the redox signal generated by analyte binding. Using this platform, we constructed and characterized two biosensors that can sense leucine and glycine, respectively. We show that these biosensors can selectively and sensitively detect their targets over a wide range of concentrations—up to 7 orders of magnitude—and that the selectivity of these sensors can be readily altered by switching the bioreceptor’s binding domain. Our work represents a new paradigm for the design of a family of modular electrochemical biosensors, where access to electrode surfaces can be controlled by protein conformational changes. American Chemical Society 2022-10-17 /pmc/articles/PMC9709943/ /pubmed/36465535 http://dx.doi.org/10.1021/jacsau.2c00291 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Murugappan, Krishnan
Sundaramoorthy, Uthayasuriya
Damry, Adam M.
Nisbet, David R.
Jackson, Colin J.
Tricoli, Antonio
Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement
title Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement
title_full Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement
title_fullStr Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement
title_full_unstemmed Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement
title_short Electrodetection of Small Molecules by Conformation-Mediated Signal Enhancement
title_sort electrodetection of small molecules by conformation-mediated signal enhancement
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709943/
https://www.ncbi.nlm.nih.gov/pubmed/36465535
http://dx.doi.org/10.1021/jacsau.2c00291
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