Synthetic polypeptide crotamine: characterization as a myotoxin and as a target of combinatorial peptides

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dc.contributorLab. Genéticapt_BR
dc.contributor.authorPompeia, Celinept_BR
dc.contributor.authorFrare, Eduardo Osóriopt_BR
dc.contributor.authorPeigneur, Stevept_BR
dc.contributor.authorTytgat, Janpt_BR
dc.contributor.authorPrieto da Silva, Álvaro Rossan de Brandãopt_BR
dc.contributor.authorOliveira, Eduardo Brandt dept_BR
dc.contributor.authorPereira, Alexandrept_BR
dc.contributor.authorKerkis, Irinapt_BR
dc.contributor.authorKolonin, Mikhail G.pt_BR
dc.date.accessioned2021-11-12T18:20:46Z-
dc.date.available2021-11-12T18:20:46Z-
dc.date.issued2021pt_BR
dc.identifier.citationPompeia C, Frare EO, Peigneur S, Tytgat J, Prieto da Silva ARB, Oliveira EB, et al. Synthetic polypeptide crotamine: characterization as a myotoxin and as a target of combinatorial peptides. J. Mol. Med.. 2021 Oct;in press. doi:10.1007/s00109-021-02140-9.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/3974-
dc.description.abstractCrotamine is a rattlesnake-derived toxin that causes fast-twitch muscle paralysis. As a cell-penetrating polypeptide, crotamine has been investigated as an experimental anti-cancer and immunotherapeutic agent. We hypothesized that molecules targeting crotamine could be designed to study its function and intervene in its adverse activities. Here, we characterize synthetic crotamine and show that, like the venom-purified toxin, it induces hindlimb muscle paralysis by affecting muscle contraction and inhibits KCNA3 (Kv1.3) channels. Synthetic crotamine, labeled with a fluorophore, displayed cell penetration, subcellular myofiber distribution, ability to induce myonecrosis, and bind to DNA and heparin. Here, we used this functionally validated synthetic polypeptide to screen a combinatorial phage display library for crotamine-binding cyclic peptides. Selection for tryptophan-rich peptides was observed, binding of which to crotamine was confirmed by ELISA and gel shift assays. One of the peptides (CVWSFWGMYC), synthesized chemically, was shown to bind both synthetic and natural crotamine and to block crotamine-DNA binding. In summary, our study establishes a functional synthetic substitute to the venom-derived toxin and identifies peptides that could further be developed as probes to target crotamine.pt_BR
dc.description.sponsorshipBovay Foundationpt_BR
dc.description.sponsorship(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológicopt_BR
dc.description.sponsorship(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulopt_BR
dc.description.sponsorship(GSK) GlaxoSmithKlinept_BR
dc.description.sponsorship(FWO) Fonds Wetenschappelijk Onderzoek - Vlaanderenpt_BR
dc.description.sponsorship(KU) Katholieke Universiteit Leuvenpt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofJournal of Molecular Medicinept_BR
dc.rightsRestricted accesspt_BR
dc.titleSynthetic polypeptide crotamine: characterization as a myotoxin and as a target of combinatorial peptidespt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1007/s00109-021-02140-9pt_BR
dc.identifier.urlhttps://doi.org/10.1007/s00109-021-02140-9pt_BR
dc.contributor.externalUniversity of Texas Health Science Centerpt_BR
dc.contributor.externalUniversity of Leuvenpt_BR
dc.contributor.external(USP) Universidade de São Paulopt_BR
dc.subject.keywordCrotaminept_BR
dc.subject.keywordMusclept_BR
dc.subject.keywordPeptidept_BR
dc.subject.keywordPhagept_BR
dc.subject.keywordMyofiberpt_BR
dc.relation.ispartofabbreviatedJ. Mol. Med.pt_BR
dc.identifier.citationabntin press, out. 2021pt_BR
dc.identifier.citationvancouver2021 Oct;in presspt_BR
dc.contributor.butantanPompeia, Celine|:Desvinculado|:Lab. Genética|:PrimeiroAutorpt_BR
dc.contributor.butantanFrare, Eduardo Osório|:Técnico|:Lab. Genéticapt_BR
dc.contributor.butantanPrieto da Silva, Álvaro Rossan de Brandão|:Pesquisador|:Lab. Genéticapt_BR
dc.contributor.butantanPereira, Alexandre|:Desvinculado|:Lab. Genéticapt_BR
dc.contributor.butantanKerkis, Irina|:Pesquisador:Docente permanente PPGTOX|:Lab. Genéticapt_BR
dc.sponsorship.butantanBovay Foundation¦¦pt_BR
dc.sponsorship.butantan(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico¦¦201949/2015–6pt_BR
dc.sponsorship.butantan(FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo¦¦2015/50040–4pt_BR
dc.sponsorship.butantanGlaxoSmithKline (GSK)¦¦pt_BR
dc.sponsorship.butantan(FWO) Fonds Wetenschappelijk Onderzoek - Vlaanderen¦¦G0E7120Npt_BR
dc.sponsorship.butantan(FWO) Fonds Wetenschappelijk Onderzoek - Vlaanderen¦¦GOC2319Npt_BR
dc.sponsorship.butantan(FWO) Fonds Wetenschappelijk Onderzoek - Vlaanderen¦¦GOA4919Npt_BR
dc.sponsorship.butantan(KU) Katholieke Universiteit Leuven¦¦PDM/19/164pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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