DNA-templated self-assembly of bradykinin into bioactive nanofibrils

Lourenço, T. C., de Mello, L. R. ORCID: https://orcid.org/0000-0001-7630-5087, Icimoto, M. Y. ORCID: https://orcid.org/0000-0002-0746-5279, Bicev, R. N. ORCID: https://orcid.org/0000-0002-5951-9005, Hamley, I. W. ORCID: https://orcid.org/0000-0002-4549-0926, Castelletto, V., Nakaie, C. R. ORCID: https://orcid.org/0000-0001-7057-1990 and da Silva, E. R. ORCID: https://orcid.org/0000-0001-5876-2276 (2023) DNA-templated self-assembly of bradykinin into bioactive nanofibrils. Soft Matter, 19 (26). pp. 4869-4879. ISSN 1744-6848 doi: 10.1039/d3sm00431g

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/112395
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Uncontrolled Keywords	Condensed Matter Physics, General Chemistry
Publisher	Royal Society of Chemistry (RSC)
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