Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin

Abstract Voltage-gated sodium (Nav) channels play a key role in generating action potentials which leads to physiological signaling in excitable cells. The availability of probes for functional studies of mammalian Nav is limited. Here, by introducing two amino acid substitutions into the beta scorp...

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Autores principales:	Tomoya Kubota, Bobo Dang, Joao L. Carvalho-de-Souza, Ana M. Correa, Francisco Bezanilla
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7170acf415be445fb7788f6811099f0f
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spelling	oai:doaj.org-article:7170acf415be445fb7788f6811099f0f2021-12-02T11:52:21ZNav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin10.1038/s41598-017-16426-x2045-2322https://doaj.org/article/7170acf415be445fb7788f6811099f0f2017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16426-xhttps://doaj.org/toc/2045-2322Abstract Voltage-gated sodium (Nav) channels play a key role in generating action potentials which leads to physiological signaling in excitable cells. The availability of probes for functional studies of mammalian Nav is limited. Here, by introducing two amino acid substitutions into the beta scorpion toxin Ts1, we have chemically synthesized a novel binder [S14R, W50Pra]Ts1 for Nav with high affinity, low dissociation rate and reduced toxicity while retaining the capability of conjugating Ts1 with molecules of interests for different applications. Using the fluorescent-dye conjugate, [S14R, W50Pra(Bodipy)]Ts1, we confirmed its binding to Nav1.4 through Lanthanide-based Resonance Energy Transfer. Moreover, using the gold nanoparticle conjugate, [S14R, W50Pra(AuNP)]Ts1, we were able to optically stimulate dorsal root ganglia neurons and generate action potentials with visible light via the optocapacitive effect as previously reported. [S14R, W50Pra]Ts1 is a novel probe with great potential for wider applications in Nav-related neuroscience research.Tomoya KubotaBobo DangJoao L. Carvalho-de-SouzaAna M. CorreaFrancisco BezanillaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tomoya Kubota Bobo Dang Joao L. Carvalho-de-Souza Ana M. Correa Francisco Bezanilla Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
description	Abstract Voltage-gated sodium (Nav) channels play a key role in generating action potentials which leads to physiological signaling in excitable cells. The availability of probes for functional studies of mammalian Nav is limited. Here, by introducing two amino acid substitutions into the beta scorpion toxin Ts1, we have chemically synthesized a novel binder [S14R, W50Pra]Ts1 for Nav with high affinity, low dissociation rate and reduced toxicity while retaining the capability of conjugating Ts1 with molecules of interests for different applications. Using the fluorescent-dye conjugate, [S14R, W50Pra(Bodipy)]Ts1, we confirmed its binding to Nav1.4 through Lanthanide-based Resonance Energy Transfer. Moreover, using the gold nanoparticle conjugate, [S14R, W50Pra(AuNP)]Ts1, we were able to optically stimulate dorsal root ganglia neurons and generate action potentials with visible light via the optocapacitive effect as previously reported. [S14R, W50Pra]Ts1 is a novel probe with great potential for wider applications in Nav-related neuroscience research.
format	article
author	Tomoya Kubota Bobo Dang Joao L. Carvalho-de-Souza Ana M. Correa Francisco Bezanilla
author_facet	Tomoya Kubota Bobo Dang Joao L. Carvalho-de-Souza Ana M. Correa Francisco Bezanilla
author_sort	Tomoya Kubota
title	Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
title_short	Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
title_full	Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
title_fullStr	Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
title_full_unstemmed	Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
title_sort	nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7170acf415be445fb7788f6811099f0f
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_version_	1718395052198199296

Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin

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