A spectroscopic investigation of the interaction between c-MYC DNA and tetrapyridinoporphyrazinatozinc(II)

Abstract

The c-MYC gene plays an important role in the regulation of cell proliferation and growth and it is overexpressed in a wide variety of human cancers. Around 90% of c-MYC transcription is controlled by the nuclease-hypersensitive element III1 (NHE III1), whose 27-nt purine-rich strand has the ability to form a G-quadruplex structure under physiological conditions. Therefore, c-MYC DNA is an attractive target for drug design, especially for cancer chemotherapy. Here, the interaction of water-soluble tetrapyridinoporphyrazinatozinc(II) with 27-nt G-rich strand (G/c-MYC), its equimolar mixture with the complementary sequence (GC/c-MYC) and related C-rich oligonucleotide (C/c-MYC) is investigated. Circular dichroism (CD) measurements of the G-rich 27-mer oligonucleotide in 150 mM KCl, pH 7 demonstrate a spectral signature consistent with parallel G-quadruplex DNA. Furthermore, the CD spectrum of the GC rich oligonucleotide shows characteristics of both duplex and quadruplex structures. Absorption spectroscopy implies that the complex binding of G/c-MYC and GC/c-MYC is a two-step process; in the first step, a very small red shift and hypochromicity and in the second step, a large red shift and hyperchromicity are observed in the Q band. Emission spectra of zinc porphyrazine are quenched upon addition of three types of DNA. According to the results of spectroscopy, it can be concluded the dominant binding mode is probably, outside binding and end stacking.

Structure-Based Virtual Screening of Novel Natural Alkaloid Derivatives as Potential Binders of h-telo and c-myc DNA G-Quadruplex Conformations

“…The current growing interest in the G4 DNA structures of promoter regions [90,91], in particular versus c-myc , led us to analyze the docking poses obtained on h-telo and c-myc receptors. With the aim to highlight the differences in the recognition of the used DNA G4 folds, we performed a contact analysis evaluating the interactions in terms of hydrogen bonds and Van der Waal’s contacts by means of Maestro graphical interface (Maestro Graphics User Interface, ver.…”

Arene Ruthenium(II) Complexes as Low-Toxicity Inhibitor against the Proliferation, Migration, and Invasion of MDA-MB-231 Cells through Binding and Stabilizing c-myc G-Quadruplex DNA

“…5 Recent studies showed that the G-rich promoter of the cmyc oncogene can form a G-quadruplex structure via a Hoogesten hydrogen bond in the presence of K + and Na + ions. 6 Complexes that can bind and stabilize G-quadruplex DNA usually exhibit excellent inhibitory activity against the growth of tumor cells. For example, porphyrin and quindoline inhibit various tumor cells by stabilizing the c-myc G-quadruplex DNA.…”

“…The in vitro and in vivo inhibitory activities of these complexes, as well as their underlying mechanisms and binding behavior to DNA molecules, have been extensively investigated. RAPTA-B ([Ru(η 6 -C 6 H 6 )(pta)-Cl 2 ]) and RAPTA-C ([Ru(η 6 -p-C 6 H 4 Me i Pr)(pta)Cl 2 ]) blocked tumor metastasis of a CBA mouse model for human breast cancer by preventing angiogenesis. 3 In addition, the arene Ru(II) complex RM175 ([(η 6 -biphenyl)Ru(ethylenediamine)-Cl] + ) inhibited tumor metastasis in vivo and blocked migration and invasion through enhancing cell−cell readhesion and down-regulated the matrix metalloproteinases (MMPs).…”

“…RAPTA-B ([Ru(η 6 -C 6 H 6 )(pta)-Cl 2 ]) and RAPTA-C ([Ru(η 6 -p-C 6 H 4 Me i Pr)(pta)Cl 2 ]) blocked tumor metastasis of a CBA mouse model for human breast cancer by preventing angiogenesis. 3 In addition, the arene Ru(II) complex RM175 ([(η 6 -biphenyl)Ru(ethylenediamine)-Cl] + ) inhibited tumor metastasis in vivo and blocked migration and invasion through enhancing cell−cell readhesion and down-regulated the matrix metalloproteinases (MMPs). 4 On the other hand, the c-myc oncogene is related to the proliferation, cell cycle arrest, metastasis, and invasion of tumor cells; this gene is located near a promoter region and is overexpressed in tumor cells, but has low expression in normal cells.…”

Porphyrins in complex with DNA: Modes of interaction and oxidation reactions

“…These derivatives are cationic phtalocyanines/porphyrazines [111,118,[126][127][128][129] or core-expanded porphyrins [130,131]. It is striking to note that negatively charged compounds such as Nmethylmesoporphyrin IX (NMM) [44,45,132,133], protoporphyrin IX [134], hemin (Fe IIIprotoporphyrin IX) [135][136][137] with two carboxylic groups or tetraphtalocyanines with four sulfonate groups [138][139][140] are endowed with G-quadruplex binding capability.…”