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Smeller László
G-quadruplexes: Thermodynamic characterization, identifying the physicochemical parameters influencing the stability

Aug 29 - kedd

15:30 – 17:00

I. Poszterszekció

P24

G-quadruplexes: Thermodynamic characterization, identifying the physicochemical parameters influencing the stability

László Smeller¹, Miklós Cervenák¹, András Végh², Orsolya R. Molnár^1, Anna Grád¹, Judit Somkuti¹

¹ Semmelweis University, Budapest, Department of Biophysics and Radiation Biology

² Semmelweis University, Budapest, Department of Ophthalmology

Besides of the well-known double-helical structures nucleic acids can form non-canonical motifs as well. The most important one is the G-Quadruplex (GQ), which is formed by guanine-rich sequences of the genome. Potentially GQ-forming sequences were found in crucial loci of the human genome, where formation of GQs can take part in the regulation of important processes like cell proliferation and cell death. Their appearance in the oncogene promoter regions made GQs an attractive target of the cancer research.

Here we report the results we obtained on two oligos, both DNA and RNA ones [1-3]. They were chosen from the genome of the hepatitis B and SARS-CoV-2 viruses. We selected a short oligo that was suggested by computer analysis of the genome to form GQ with high probability.

Infrared and fluorescence spectroscopic methods have been used to determine the conformation of the GQs. Förster resonance energy transfer allowed following the unfolding of the oligos.

Since GQs were considered as targets of the cancer therapy, several ligands were developed for stabilization of the human GQs. We investigated three of these ligands, whether they can stabilize the viral GQs as well.

As conclusion, we have proven that both HepB (DNA) and C19/1 (RNA) viral oligos form G-quadruplex structure however with different temperature stability. The unfolding mid-points were 53 and 37 °C respectively.

All the ligands we investigated (TMPyP4, BRACO19, PhenDC3) were proven to bind and stabilize these oligos (except BRACO19 which did not bind C19/1).

These results might have important impact in the fighting against viruses, since stabilization of the GQs will influence the proliferation of the virus.

Acknowledgment

The authors thank for the support from NFKI K-124697 and TKP2021-EGA-23 grants.

References

[1] Molnár, OR., et al.,(2021) Scientific Reports (2021) 11:23243
[2] Somkuti, J., et al.,(2021) Biology 10:1173;
[3] Smeller, L., (2023) Int. J. Mol. Sci. 24:1803