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

Autor(es)

de Carvalho Porta, Lucas ^[1] ; Fadel, Valmir ^[2] ; D'Arc Campeiro, Joana ^[1] ; Oliveira, Eduardo Brandt ^[3] ; Godinho, Rosely Oliveira ^[1] ; Hayashi, Mirian Akemi Furuie ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, Dept Farmacol, Escola Paulista Med EPM, Rua 3 Maio 100, Ed INFAR, 3rd Floor, BR-04044020 Sao Paulo - Brazil

^[2] Univ Estadual Sao Paulo UNESP, Sao Jose Do Rio Preto - Brazil

^[3] Univ Sao Paulo USP FMRP, Dept Bioquim & Imunol, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF MOLECULAR MEDICINE-JMM; v. 98, n. 11 SEP 2020.
• Citações Web of Science: 0

Resumo

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 center dot Synthetic crotamine showed ex vivo and in vivo activities similar to native peptide. center dot Synthetic crotamine structure conservation was demonstrated by NMR analysis. center dot Synthetic crotamine is able to transfect and transport DNA into eukaryotic cells. center dot Synthetic crotamine shows tumor growth inhibition in vivo. center dot Synthetic crotamine increases survival of mice bearing tumor. (AU)

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