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Dializa równowagowa. Metoda badania selektywności oddziaływań ligand.DNA

Czerwińska I., Głuszyńska A., Juskowiak B.

Wiadomości Chemiczne

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2010

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[Z] 64, 1-2

105-122

EN

Equilibrium or competition dialysis is a powerful tool for binding study of ligands that are expected to bind to nucleic acids with selectivity related to their structure or sequence. In the equilibrium dialysis experiment, a set of nucleic acid samples that differ in structure and sequence is dialyzed against a test ligand solution. After equilibration, the concentration of ligand bound to each structure or sequence is determined by UV-Vis absorption or fluorescence spectroscopy in each dialysis unit. Since all nucleic acid samples are in equilibrium with the same free ligand concentration, the amount of bound ligand is directly related to the ligand binding affinity. Thus, equilibrium provides a direct measure of selectivity and identifies the nucleic acid sample, which is preferred by a particular ligand. We describe here the principles and practice of the method. Examples of an application of the method are limited to the discovery of small molecules that selectively recognize the unique structural features of G-quadruplexes. There are proofs for important functional roles of G-quadruplex structures in biology (maintenance of telomeres, transcriptional regulation, and modulation of mRNA translation). G-quadruplex DNA can exist in a variety of structural forms that may possess numerous potential binding sites for small molecules. Therefore equilibrium dialysis provides a useful tool for discovery of new mall-molecule therapeutic agents targeting G-quadruplexes.

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Preferential Binding of Arylstilbazolium Ligands to Guanine Quadruplexes

Czerwińska I., Juskowiak B.

Polish Journal of Chemistry

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2009

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Vol. 83, nr 6

1227-1230

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Procesy przenoszenia energii (FRET) w badaniach czteroniciowych form DNA

Juskowiak B., Gałęzowska E., Paczesny J.

Wiadomości Chemiczne

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2006

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[Z] 60, 7-8

547-566

EN

DNA sequences with stretches of multiple guanines can form four-stranded tetraplex DNA structures called guanine-quadruplexes or G4 DNA. They contain stacked arrays of planar guanine quartets linked by connecting loops. Evidence supports the occurrence of quadruplexes in the cell nucleus and a number of biological functions have been attributed to quadruplexes. In eukaryotic systems guanine-rich sequences are positioned at the ends of chromosomes and are called tclomcric DNA. The study of telomeric DNA has acquired importance through the discovery of the relationship between telomerase activity in most cancer cells and telomere folding into tetraplex structure. Coordination of certain metal cations stabilizes G-quadruplex as do some promising small organic molecules, which are regarded as potential anticancer drugs. Among many techniques employed to explore properties of G-quadrupIexes, fluorescence resonance energy transfer (FRET) has been recognized as a powerful tool to explore tetraplex formation due to extreme sensitivity and the distance dependency of the FRET process. This review shows how FRET contributes to G-quadruplex research and focuses on the FRET application, describing briefly also the underlying principles. Information about molecular structure, binding events, and motion are considered to be potentially available from FRET measurements. In a typical FRET experiment a guanine-rich oligonucleotide labeled with proper fluorophores (FRET donor and acceptor) undergoes structural transformations (folding or unfolding), which are monitored by spectral changes in the fluorescence spectra of FRET partners. We tried to summarize the current developments in the field of the various applications of FRET measurements for the fundamental structural and kinetic investigations of G-quadru-plexes and their complexes with metal cations and organic ligands. Fundamental applications include studies of quadruplex unfolding kinetics with the use of complementary DNA or PNA (Peptide Nucleic Acid) strands as a duplex trap or determination of thermodynamic parameters. Practical applications are illustrated by the FRET-based selection of quadruplex-binding ligands, construction of the quadruplex-based nanomotor, design of molecular probes for protein recognition, and development of sensors for the detection of potassium ions in aqueous media. The presented examples of FRET studies showed that FRET is particularly use ful in structural studies of oligonucleotides capable of folding into tetraplex structure.

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Interactions of the Oxidation Products of Papaverine with Guanine Quadruplexes

Mądry L., Gałęzowska E., Głuszyńska A., Hermann T., Zabel M., Juskowiak B.

Polish Journal of Chemistry

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2006

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Vol. 80, nr 6

921-929

EN

The interactions of G-quadruplex DNA with two oxidation products of papaverine, 6a,12a-diazadibenzo-[a,g]fluorenylium derivative (1) and 2,3,9,10-tetramethoxy-12- oxo-12H-indolo[2,1-a]isoquinolinium cation (2) were investigated. Effect of the organic modifier (EtOH) and NaCl on the spectral properties and aggregation of free ligands and on the DNA-binding affinity were assessed. Ligand 1 exhibited tendency for aggregation and showed higher binding selectivity for G-quadruplex DNA over double-stranded DNA. Both ligands were capable of interacting with DNA according to three binding modes: (i) electrostatic interactions, (ii) classical intercalation to dsDNA, and (iii) the specific binding to quadruplex DNA. The cytotoxic activity of ligand 2 was generally higher than that for ligand 1, approaching a micromolar concentration level that may suggest its telomerase inhibition activity.

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Spectral Properties and DNA-binding Study of 6a, 12a-Diazadibenzo-[a,g]fluorenylium Derivative

Juskowiak B., Gałęzowska E., Kościelna H., Hermann T., Piotrowska K.

Polish Journal of Chemistry

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2005

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Vol. 79 / nr 5

831-844

EN

The DNA binding affinity and anion effect on the aggregation of a G-quadruplex selective ligand, 6a,12a-diazadibenzo-[a,g]fluorenylium derivative, were studied by UV-Vis absorption, molecular modeling and fluorescence spectroscopy. The anion character and its concentration influenced the spectral properties of ligand aggregates. Observed spectral peculiarities were discussed in terms of the formation of H- and J-type aggregates. The DNA binding mode and affinity of the ligand depended on the salt concentration; preferential binding to G-quadruplexDNAwas clearly seen at higher salt concentration.

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DNA Changes Dramatically Photoisomerization of Arylstilbazolium Ligands

Juskowiak B.

Polish Journal of Chemistry

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2004

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Vol. 78 / nr 2

319-321

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DNA Effect on the Photoisomerization of Naphthalenevinylpyridinium Derivatives

Chudak M., Juskowiak B.

Polish Journal of Chemistry

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2003

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Vol. 77 / nr 3

303-313

EN

The binding study, photoisomerization and spectral behavior of novel DNA interacting dyes, 1-[2-(N-methylpyridinium-4-yl)vinyl]naphthalene iodide (1) and 2-[2-(N-methylpyridinium- 4-yl)vinyl]naphthalene iodide (2), are reported. Ligand-DNA interactions were investigated by UV-Vis absorption and circular dichroism measurements. The ligands have different binding characteristics, depending on the structure of the isomers. The nonplanar cis isomers have lower affinity to DNA. Photoisomerization experiments in the absence and the presence of DNA showed significant differences in the composition of resulting photostationary states (pss). The lower values of pss in the presence of DNAindicate that trans _ cisisomerization of DNA-bound ligands is suppressed, which leads finally to trans isomer-rich pss. Moreover, the quantum yield of trans _ cis photoisomerization (_TC) decreased dramatically.

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Photoisomerizable DNA Ligands. Photoisomerization of Anthrylvinylpyridinium Derivatives

Juskowiak B., Chudak M., Takagi N., Takagi M.

Polish Journal of Chemistry

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2002

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Vol. 76 / nr 1

83-93

EN

Two potential DNA intercalators capable of cis_trans isomerization, 9-[2-(N-methylpyridinium- 4-yl)vinyl]anthracene (1) and 9,10-bis [2-(N-methylpyridinium-4-yl)vinyl] anthracene (2), have been prepared, characterized and their spectral and photoisomerization behavior have been studied. Both ligands exhibit low fluorescence quantum yields in aqueous solution and substantial enhancement of emission in the presence of DNA. Two-way isomerization was observed for 1, while trans_cis process appeared to be inefficient for ligand 2. An intramolecular charge transfer excited state was suggested to explain the differences in spectral behavior and photoisomerization of ligands.

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Energy Transfer Evidence for Cross-linking of DNA by 1,4-Bis((N-methylquinolinium-4-yl)vinyl) Benzene

Juskowiak B.

Polish Journal of Chemistry

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2001

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Vol. 75, nr 9

1377-1379