DNA-templated self-assembly of bradykinin into bioactive nanofibrils

Autor(es)

Lourenco, Thiago C. ; de Mello, Lucas R. ; Icimoto, Marcelo Y. ; Bicev, Renata N. ; Hamley, Ian W. ; Castelletto, Valeria ; Nakaie, Clovis R. ; da Silva, Emerson R.

• Tipo de documento: Artigo Científico
• Fonte: SOFT MATTER; v. 19, n. 26, p. 11-pg., 2023-06-12.

Resumo

Bradykinin (BK) is a peptide hormone that plays a crucial role in blood pressure control, regulates inflammation in the human body, and has recently been implicated in the pathophysiology of COVID-19. In this study, we report a strategy for fabricating highly ordered 1D nanostructures of BK using DNA fragments as a template for self-assembly. We have combined synchrotron small-angle X-ray scattering and high-resolution microscopy to provide insights into the nanoscale structure of BK-DNA complexes, unveiling the formation of ordered nanofibrils. Fluorescence assays hint that BK is more efficient at displacing minor-groove binders in comparison with base-intercalant dyes, thus, suggesting that interaction with DNA strands is mediated by electrostatic attraction between cationic groups at BK and the high negative electron density of minor-grooves. Our data also revealed an intriguing finding that BK-DNA complexes can induce a limited uptake of nucleotides by HEK-293t cells, which is a feature that has not been previously reported for BK. Moreover, we observed that the complexes retained the native bioactivity of BK, including the ability to modulate Ca2+ response into endothelial HUVEC cells. Overall, the findings presented here demonstrate a promising strategy for the fabrication of fibrillar structures of BK using DNA as a template, which keep bioactivity features of the native peptide and may have implications in the development of nanotherapeutics for hypertension and related disorders. (AU)

• Processo FAPESP: 21/04885-3 - Síntese e investigação estrutural de peptídeos e de polímeros: da inovações no método da síntese ao estudo de alguns peptídeos de relevância fisiológica
• Beneficiário: Clovis Ryuichi Nakaie
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 22/03056-6 - Caracterização ultraestrutural de nanoscaffolds bioativos
• Beneficiário: Emerson Rodrigo da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Projeto Inicial
• Processo FAPESP: 19/19719-1 - Matrizes peptídicas bioativas: da estrutura molecular às aplicações biomédicas
• Beneficiário: Lucas Rodrigues de Mello
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 21/10092-6 - Desenvolvimento de matrizes peptídicas bioativas: da estrutura molecular às aplicações biomédicas
• Beneficiário: Lucas Rodrigues de Mello
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado