Nemorubicin and doxorubicin bind the G-quadruplex sequences of the human telomeres and of the c-MYC promoter element Pu22

Scaglioni, Leonardo; Mondelli, R.; Artali, Roberto; Sirtori, Federico Riccardi; Mazzini, Stefania

doi:10.1016/j.bbagen.2016.02.011

Cited by 45 publications

(40 citation statements)

References 57 publications

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“…The analysis of the spectra at R=3.0 was performed starting from the attribution of the three tetrads by inter-residue NOE connectivities between the H1 imino and the aromatic protons H8 of guanine residues (following the procedure used for the study of other ligands. 28,52 The results reported in Table S6 show that the quadruplex structure is conserved. Also, for these complexes a significant shielding was observed for the H1 imino protons of the internal tetrad (δ = -0.30/-0.60 ppm) although lower than the values of the external tetrads (δ ≥-0.60 ppm).…”

Section: Determination Of Dna:ligand Stoichiometrymentioning

confidence: 95%

“…In this work, a set of different DNA sequences (Table 1) representing several nucleic acid structures was used. 16,25,28,42 T20 was used as model for an unfolded single-stranded DNA sequence. As models of dsDNA, the self-complementary sequences Dickerson-Drew dodecamer and a 26-mer hairpin (ds26) were used.…”

Section: Selectivitymentioning

confidence: 99%

“…Recently, it has been reported that Pu22-14T23T gives the same interactions with ligands as wild type Pu22. 28,29 In this work, the interaction of six natural benzo[c]phenanthridine alkaloids (macarpine, sanguilutine, sanguirubine, chelerythrine, sanguinarine and chelirubine) with GQ DNA structures formed by HT22, c-kit21T21, c-kit21T12T21 and Pu22T14T23 sequences was studied. Circular dichroism, spectroscopically-monitored melting experiments and fluorescence titrations, competitive dialysis and nuclear magnetic resonance spectroscopy were used with this purpose.…”

Section: Introductionmentioning

confidence: 99%

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Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively stabilize G-quadruplexes

Jarošová

Paroulek

Rájecký

et al. 2018

Phys. Chem. Chem. Phys.

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In this work, the interaction of six natural benzo[c]phenanthridine alkaloids (macarpine, sanguilutine, sanguirubine, chelerythrine, sanguinarine and chelirubine) with parallel and antiparallel G-quadruplex DNA structures was studied. HT22 corresponding to the end of human telomeres and the modified promoter oncogene c-kit21 and Pu22 sequences have been used. Spectroscopically-monitored melting experiments and fluorescence titrations, competitive dialysis and nuclear magnetic resonance spectroscopy were used for this purpose. The results showed that these alkaloids stabilized G-quadruplex structures in terms of increments of Tm values (from 15 to 25 °C) with high selectivity over duplexes and unfolded DNA. The mode of binding was mainly by stacking on the terminal G-tetrads with stoichiometries of 1 : 2 (DNA : ligand). The presence of non-specific electrostatic interactions was also observed. Overall, the results pointed to a strong stabilization of G-quadruplex structures by these alkaloids.

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Section: Determination Of Dna:ligand Stoichiometrymentioning

confidence: 95%

Section: Selectivitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively stabilize G-quadruplexes

Jarošová

Paroulek

Rájecký

et al. 2018

Phys. Chem. Chem. Phys.

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“…Therefore, the oncogene c-myc G-quadruplex DNA as a potential target for antitumor drugs has received increased attention. Up to now, a number of ruthenium(II) complexes have been reported to effectively bind to, induce and stabilize c-myc G-quadruplex DNA [11,[20][21][22][23][24][25][26][27]. Zhang However, among the ruthenium(II) complexes reported, limited investigations are focused on the binuclear complexes.…”

Section: Introductionmentioning

confidence: 99%

“…The IC50 values of the ruthenium complex toward different cell lines. 26. 18.27 ± 0.75 13.47 ± 0.26 12.05 ± 0.03 20.72 ± 1.23…”

mentioning

confidence: 99%

Induction of C-Myc G-Quadruplex Dna and Cytotoxicity of a Calix[]arene-Containing Binuclear Ruthenium(ii) Complex

Wang

Yan

et al. 2019

J. Chil. Chem. Soc.

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Herein, a binuclear ruthenium(II) complex modified by calix[4]arene group has been prepared. The complex as potential inducer and stabilizer of c-myc Gquadruplex DNA and antitumor reagent were studied. Observations revealed that the complex could bind to c-myc Pu27 and Pu22 DNA strongly with constants of 1.18 × 10 7 (Pu27) and 4.13 × 10 6 M-1 (Pu22) via groove mode as determined from absorption and luminescence titrations, as well as CD spectra. Results of continuous variation analysis confirmed that the complex interacted with c-myc G-quadruplex DNA through a 1:1 binding stoichiometry. As verified by PCR-stop assay, the replication of c-myc DNA was effectively blocked by the complex with the complete inhibition at the complex concentration of 4.0 μM both for Pu27 and Pu22, suggesting that the complex could efficiently induce the formation of c-myc G-quadruplex DNA. The appearance of blue TMB solution in the visual experiment also proved that the sequences of Pu27 and Pu22 could fold into G-quadruplex under the induction of the complex. Nevertheless, the complex was found to exhibit weak stabilization ability on c-myc G-quadruplex DNA according to FRET assay, which increased the melting point of c-myc DNA only 3-3.5 °C. The experiments on Topoisomerase inhibition and cytotoxicity of the complex showed that it acted as an inhibitor of TopoI and exhibited moderate anticancer activity against MCF-7 and Huh-7 tumor cells.

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Quadruplex–Duplex Junction: A High‐Affinity Binding Site for Indoloquinoline Ligands

Vianney

Preckwinkel

Mohr

et al. 2020

Chemistry A European J

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A parallel quadruplex derived from the Myc promoter sequence was extended by a stem‐loop duplex at either its 5′‐ or 3′‐terminus to mimic a quadruplex–duplex (Q–D) junction as a potential genomic target. High‐resolution structures of the hybrids demonstrate continuous stacking of the duplex on the quadruplex core without significant perturbations. An indoloquinoline ligand carrying an aminoalkyl side chain was shown to bind the Q–D hybrids with a very high affinity in the order Ka≈107 m−1 irrespective of the duplex location at the quadruplex 3′‐ or 5′‐end. NMR chemical shift perturbations identified the tetrad face of the Q–D junction as specific binding site for the ligand. However, calorimetric analyses revealed significant differences in the thermodynamic profiles upon binding to hybrids with either a duplex extension at the quadruplex 3′‐ or 5′‐terminus. A large enthalpic gain and considerable hydrophobic effects are accompanied by the binding of one ligand to the 3′‐Q–D junction, whereas non‐hydrophobic entropic contributions favor binding with formation of a 2:1 ligand‐quadruplex complex in case of the 5′‐Q–D hybrid.

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Nemorubicin and doxorubicin bind the G-quadruplex sequences of the human telomeres and of the c-MYC promoter element Pu22

Cited by 45 publications

References 57 publications

Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively stabilize G-quadruplexes

Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively stabilize G-quadruplexes

Induction of C-Myc G-Quadruplex Dna and Cytotoxicity of a Calix[]arene-Containing Binuclear Ruthenium(ii) Complex

Quadruplex–Duplex Junction: A High‐Affinity Binding Site for Indoloquinoline Ligands

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