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1.
Int J Mol Sci ; 25(5)2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38473730

RESUMO

The G-quadruplex is one of the non-canonical structures formed by nucleic acids, which can be formed by guanine-rich sequences. They became the focus of much research when they were found in several oncogene promoter regions and also in the telomeres. Later on, they were discovered in viruses as well. Various ligands have been developed in order to stabilize DNA G-quadruplexes, which were believed to have an anti-cancer or antiviral effect. We investigated three of these ligands, and whether they can also affect the stability of the G-quadruplex-forming sequences of the RNA genome of SARS-CoV-2. All three investigated oligonucleotides showed the G-quadruplex form. We characterized their stability and measured their thermodynamic parameters using the Förster resonance energy transfer method. The addition of the ligands caused an increase in the unfolding temperature, but this effect was smaller compared to that found earlier in the case of G-quadruplexes of the hepatitis B virus, which has a DNA genome.


Assuntos
Acridinas , COVID-19 , Compostos de Anéis Fundidos , Quadruplex G , Porfirinas , Humanos , SARS-CoV-2
2.
Sci Rep ; 11(1): 23243, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34853392

RESUMO

Specific guanine rich nucleic acid sequences can form non-canonical structures, like the four stranded G-quadruplex (GQ). We studied the GQ-forming sequence (named HepB) found in the genome of the hepatitis B virus. Fluorescence-, infrared- and CD-spectroscopy were used. HepB shows a hybrid form in presence of K+, but Na+, Li+, and Rb+ induce parallel structure. Higher concentrations of metal ions increase the unfolding temperature, which was explained by a short thermodynamic calculation. Temperature stability of the GQ structure was determined for all these ions. Na+ has stronger stabilizing effect on HepB than K+, which is highly unusual. The transition temperatures were 56.6, 53.8, 58.5 and 54.4 °C for Na+, K+, Li+, and Rb+ respectively. Binding constants for Na+ and K+ were 10.2 mM and 7.1 mM respectively. Study of three ligands designed in cancer research for GQ targeting (TMPyP4, BRACO19 and PhenDC3) showed unequivocally their binding to HepB. Binding was proven by the increased stability of the bound form. The stabilization was higher than 20 °C for TMPyP4 and PhenDC3, while it was considerably lower for BRACO19. These results might have medical importance in the fight against the hepatitis B virus.


Assuntos
Acridinas/metabolismo , Compostos de Anéis Fundidos/metabolismo , Quadruplex G , Vírus da Hepatite B/genética , Porfirinas/metabolismo , Acridinas/química , DNA/química , Compostos de Anéis Fundidos/química , Genoma Viral , Vírus da Hepatite B/química , Vírus da Hepatite B/metabolismo , Ligantes , Porfirinas/química , Termodinâmica
3.
Biology (Basel) ; 10(11)2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34827166

RESUMO

G-quadruplexes are noncanonical structures formed by guanine-rich sequences of the genome. They are found in crucial loci of the human genome, they take part in the regulation of important processes like cell proliferation and cell death. Much less is known about the subjects of this work, the viral G-quadruplexes. We have chosen three potentially G-quadruplex-forming sequences of hepatitis B. We measured the stability and the thermodynamic parameters of these quadruplexes. We also investigated the potential stabilization of these G-quadruplexes by binding a special ligand that was originally developed for cancer therapy. Fluorescence and infrared spectroscopic measurements were performed over wide temperature and pressure ranges. Our experiments indicate the small unfolding volume change of all three oligos. We found a difference between the unfolding of the 2-quartet and the 3-quartet G-quadruplexes. All three G-quadruplexes were stabilized by TMPyP4, which is a cationic porphyrin developed for stabilizing the human telomere.

4.
Heliyon ; 6(12): e05702, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33354631

RESUMO

G-quadruplexes are tetrahelical structures. They are important targets for anti-cancer drugs, since they are situated at crucial positions within the genome. We studied the volumetric properties of the unfolding of three G-quadruplexes in the presence of potassium ion. The unfolding volume changes were determined using high-pressure fluorescence spectroscopy. The c-MYC, KIT, and VEGF sequences unfold with the transition volume of -17, -6 and -18 cm3/mol, respectively. The small magnitude of the unfolding volume of KIT could be explained by its unique structure and the lower amount of void volume. Since the cell interior is highly crowded, the available volume is restricted. Therefore the volumetric changes during the conformational transformations gain biological importance.

5.
Phys Chem Chem Phys ; 22(41): 23816-23823, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-33064110

RESUMO

Cytosine rich DNA sequences can fold into a non-canonical four stranded intercalated i-motif structure. We investigated Htel-iM, an i-motif structure of the human telomeric DNA region that plays an important role in cell division, cancer diseases and aging. A high pressure up to 1 Gpa was applied to reveal the volumetric changes during unfolding. Thermal transitions at different pressures were followed by infrared and fluorescence spectroscopy. We demonstrated that Htel-iM unfolds in two steps. First the outer hydrogen bonds break in which C(2)[double bond, length as m-dash]O(2) and the N(4)H2 amino group is involved, subsequently the hydrogen bond involving N(3)+ becomes broken. Htel-iM was destabilized by pressure and unfolded with a negative volume change.


Assuntos
DNA/química , Humanos , Ligação de Hidrogênio , Concentração de Íons de Hidrogênio , Conformação de Ácido Nucleico , Motivos de Nucleotídeos , Pressão , Temperatura
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