Biophysical and pharmacological characterization of a full-length synthetic analog of the antitumor polypeptide crotamine

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Autor(es): dc.contributorUniversidade Federal de São Paulo (UNIFESP)-
Autor(es): dc.contributorUniversidade Estadual Paulista (Unesp)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorde Carvalho Porta, Lucas-
Autor(es): dc.creatorFadel, Valmir [UNESP]-
Autor(es): dc.creatorD’Arc Campeiro, Joana-
Autor(es): dc.creatorOliveira, Eduardo Brandt-
Autor(es): dc.creatorGodinho, Rosely Oliveira-
Autor(es): dc.creatorHayashi, Mirian Akemi Furuie-
Data de aceite: dc.date.accessioned2022-02-22T00:32:47Z-
Data de disponibilização: dc.date.available2022-02-22T00:32:47Z-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2020-12-11-
Data de envio: dc.date.issued2019-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1007/s00109-020-01975-y-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/201162-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/201162-
Descrição: dc.descriptionAbstract: Crotamine is a polypeptide isolated from the venom of a South American rattlesnake. Among the properties and biological activities of crotamine, the most extraordinary is its ability to enter cells with unique selective affinity and cytotoxic activity against actively proliferating cells, such as tumor cells. This peptide is also a cargo carrier, and anticipating commercial application of this native polypeptide as a potential theranostic compound against cancer, we performed here a side-by-side characterization of a chemically synthesized full-length crotamine compared with its native counterpart. The structural, biophysical, and pharmacological properties were evaluated. Comparative NMR studies showed structural conservation of synthetic crotamine. Moreover, similarly to native crotamine, the synthetic polypeptide was also capable of inhibiting tumor growth in vivo, increasing the survival of mice bearing subcutaneous tumor. We also confirmed the ability of synthetic crotamine to transfect and transport DNA into eukaryotic cells, in addition to the importance of proteoglycans on cell surface for its internalization. This work opens new opportunities for future evaluation of chimeric and/or point-mutated analogs of this snake polypeptide, aiming for improving crotamine properties and applications, as well as possibly diminishing its potential toxic effects. Key messages: • Synthetic crotamine showed ex vivo and in vivo activities similar to native peptide. • Synthetic crotamine structure conservation was demonstrated by NMR analysis. • Synthetic crotamine is able to transfect and transport DNA into eukaryotic cells. • Synthetic crotamine shows tumor growth inhibition in vivo. • Synthetic crotamine increases survival of mice bearing tumor.-
Descrição: dc.descriptionDepartamento de Farmacologia Escola Paulista de Medicina (EPM) Universidade Federal de São Paulo (UNIFESP), Rua 3 de maio 100, Ed. INFAR, 3rd floor-
Descrição: dc.descriptionUniversidade Estadual de São Paulo (UNESP)-
Descrição: dc.descriptionDepartamento de Bioquímica e Imunologia Universidade de São Paulo (USP-FMRP)-
Descrição: dc.descriptionUniversidade Estadual de São Paulo (UNESP)-
Idioma: dc.languageen-
Relação: dc.relationJournal of Molecular Medicine-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectCPP-
Palavras-chave: dc.subjectCrotamine-
Palavras-chave: dc.subjectHind limb paralysis-
Palavras-chave: dc.subjectMelanoma tumor-
Palavras-chave: dc.subjectProteoglycans-
Palavras-chave: dc.subjectSkeletal muscle contraction-
Palavras-chave: dc.subjectStructural NMR-
Título: dc.titleBiophysical and pharmacological characterization of a full-length synthetic analog of the antitumor polypeptide crotamine-
Tipo de arquivo: dc.typelivro digital-
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