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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Nature Portfolio
2017
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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) |
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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 |
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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 |
work_keys_str_mv |
AT tomoyakubota navchannelbindercontainingaspecificconjugationsitebasedonalowtoxicitybscorpiontoxin AT bobodang navchannelbindercontainingaspecificconjugationsitebasedonalowtoxicitybscorpiontoxin AT joaolcarvalhodesouza navchannelbindercontainingaspecificconjugationsitebasedonalowtoxicitybscorpiontoxin AT anamcorrea navchannelbindercontainingaspecificconjugationsitebasedonalowtoxicitybscorpiontoxin AT franciscobezanilla navchannelbindercontainingaspecificconjugationsitebasedonalowtoxicitybscorpiontoxin |
_version_ |
1718395052198199296 |