Postsynthetic Modification of Oligonucleotides with Imidazophenazine Dye and its Effect on Duplex Stability

Dubey, L. V.; Ryazanova, Olga; Zozulya, Victor; Fedoryak, D. M.; Dubey, I. Ya.

doi:10.1080/15257770.2011.598489

Cited by 5 publications

(5 citation statements)

References 38 publications

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“…Briefly, tris(4-pyridyl)phenylporphine containing a carboxybutyl function [35] was conjugated to N 1 -aminoalkyl derivative of imidazo [4,5-b]phenazine in the presence of BOP-HOBT coupling reagent, followed by N-methylation of pyridine residues by methyl iodide. Imidazo [4,5-b]phenazine dye and its aminoalkyl derivatives were obtained in accordance with methods reported in [36]. Poly(G) polynucleotide from Sigma Chem.…”

Section: Methodsmentioning

confidence: 99%

Spectroscopic Studies on Binding of Porphyrin-Phenazine Conjugate to Four-Stranded Poly(G)

et al. 2015

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Binding of a novel cationic porphyrin-imidazophenazine conjugate, TMPyP(3+)-ImPzn, to four-stranded poly(G) was investigated in aqueous solutions of neutral pH under near physiological ionic conditions using absorption, polarized fluorescent spectroscopy and fluorescence titration techniques. In absence of the polymer the conjugate folds into stable internal heterodimer with stacking between the porphyrin and phenazine chromophores. Binding of TMPyP(3+)-ImPzn to poly(G) is realized by two competing ways. At low polymer-to-dye ratio (P/D < 6) outside electrostatic binding of the cationic porphyrin moieties of the conjugate to anionic polynucleotide backbone with their self-stacking is predominant. It is accompanied by heterodimer dissociation and distancing of phenazine moieties from the polymer. This binding mode is characterized by strong quenching of the conjugate fluorescence. Increase of P/D results in the disintegration of the porphyrin stacks and redistribution of the bound conjugate molecules along the polymer chain. At P/D > 10 another binding mode becomes dominant, embedding of TMPyP(3+)-ImPzn heterodimers into poly(G) groove as a whole is occurred.

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Section: Methodsmentioning

confidence: 99%

Spectroscopic Studies on Binding of Porphyrin-Phenazine Conjugate to Four-Stranded Poly(G)

et al. 2015

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“…Porphyrin ring was then metalated by heating with zinc acetate in demethylformamide-collidine mixture [41]. Imidazo [4,5-b]phenazine dye and its aminoalkyl derivatives were obtained in accordance with methods reported in [42]. Poly(G) polynucleotide from Sigma Chem.…”

Section: Methodsmentioning

confidence: 99%

Binding of Metallated Porphyrin-Imidazophenazine Conjugate to Tetramolecular Quadruplex Formed by Poly(G): a Spectroscopic Investigation

et al. 2015

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The binding of telomerase inhibitor ZnTMPyP(3+)-ImPzn, Zn(II) derivative of tricationic porphyrin-imidazophenazine conjugate, to tetramolecular quadruplex structure formed by poly(G) was studied in aqueous solutions at neutral pH and near physiological ionic strength using absorption and polarized fluorescent spectroscopy techniques. Three binding modes were determined from the dependences of the fluorescence intensity and polarization degree for the porphyrin and phenazine moieties of the conjugate on molar polymer-to-dye ratio (P/D). The first one is outside electrostatic binding of positively charged porphyrin fragments to anionic phosphate groups of the polymer which prevails only at very low P/D values and manifests itself by substantial fluorescence quenching. It is suggested that the formation of externally bound porphyrin dimers occurs. The other two binding modes observed at high P/D are embedding of the ZnTMPyP(3+) moiety into the groove of poly(G) quadruplex accompanied by more than 3-fold enhancement of the conjugate emission, and simultaneous intercalation of the phenazine fragment between the guanine bases accompanied by the increase of its fluorescence polarization degree up to 0.25. Thus Zn(II) conjugate seems to be promising ligand for the stabilization of G-quadruplex structures since porphyrin binding to poly(G) is strengthened by additional intercalation of phenazine moiety.

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“…В работах [55][56][57][58][59] методами молекулярной спектроскопии и термической денатурации с регистрацией по поглощению и флуоресценции изучены комплексы антисмысловых олигонуклеотидов (dT) n (n = 10, 14, 15), модифицированных имидазофеназиновым производным F1rib, с комплементарными биополимерамимишенями: олигонуклеотидом (dA) 15 , однонитевыми полинуклеотидами poly(rA), poly(dA), двухнитевым poly(dA)⋅poly(dT). Установлено, что ковалентное присоединение красителя к 3 ' -концу олигонуклеотидной последовательности существенно повышает термостабильность образуемых двух-и трехспиральных структур за счет интеркаляции хромофора между плоскостями адениновых оснований, что обеспечивает дополнительную энергию связывания (рис.…”

Section: влияние феназинового красителя ковалентно присоединенного к концу антисмыслового олигонуклеотида на стабильность образуемых им дunclassified

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

2019

Biophysical Bulletin

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Background: Determination of molecular mechanisms of action of drugs forms a scientific basis for the directed search of efficient medications. Assumed pathways of interactions of chemotherapeutic drugs which affect infectious agents and malignant neoplasm with their potential molecular targets require direct evidences at the molecular level. Such evidences can be obtained by means of molecular biophysics which possesses an arsenal of new powerful physical techniques for studying the intermolecular interactions of biomolecules and pharmaceutical agents. Objectives: The aim of this review is the generalization of the results of long standing investigations on the molecular mechanisms of action of chemotherapeutic agents performed in the biophysical departments of B. Verkin Institute for Low Temperature Physics and Engineering (ILTPE) of the NAS of Ukraine. The first part of the review is devoted to anticancer and antiviral agents targeted presumably at nucleic acids. Materials and methods: Mass spectrometric studies of molecules of thermally unstable drugs and their complexes with biomolecules have been advanced significantly due to the development of soft ionization/desorption techniques; the researchers of ILTPE have made noticeable contribution to this field. The methods of molecular spectroscopy and computer modeling by means of quantum chemistry were applied in the combined investigations. Results: The objects of study were the systems composed of chemotherapeutic drugs – thiophosphamide, phenazine derivatives and phenazine-modified antigene/antisense oligonucleotides, quaternary compounds, tilorone – and their molecular targets – DNA, oligo- and polynucleotides and nucleic acids components. The mechanisms of action of these drugs established at the model molecular level consisted in the specific and nonspecific noncovalent or covalent interactions of the drugs’ molecules with nucleic acids and their components and in the formation of stable drug-target complexes. Conclusions: The experience of investigations conducted during several decades at the ILTPE has demonstrated the efficiency of the application of the methods and approaches of molecular biophysics to establishing of molecular mechanisms of drugs action. The basic results obtained are of practical importance for the further development of new efficient pharmaceuticals.

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Postsynthetic Modification of Oligonucleotides with Imidazophenazine Dye and its Effect on Duplex Stability

Cited by 5 publications

References 38 publications

Spectroscopic Studies on Binding of Porphyrin-Phenazine Conjugate to Four-Stranded Poly(G)

Spectroscopic Studies on Binding of Porphyrin-Phenazine Conjugate to Four-Stranded Poly(G)

Binding of Metallated Porphyrin-Imidazophenazine Conjugate to Tetramolecular Quadruplex Formed by Poly(G): a Spectroscopic Investigation

Biophysical investigations of molecular mechanisms of chemotherapeutic agents action. 1. Chemotherapeutic and antiviral agents (Review)

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