DNA structural features responsible for sequence-dependent binding geometries of Hoechst 33258

Moon, Jin-Hee; Kim, Seog K.; Sehlstedt, Ulrica; Rodger, Alison; Nordén, Bengt

doi:10.1002/(sici)1097-0282(199605)38:5<593::aid-bip5>3.0.co;2-n

Cited by 42 publications

(38 citation statements)

References 33 publications

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“…1,2) Several high resolution crystal and NMR structures have been determined for these ligands bound to short oligonucleotides and provide valuable insights into the details of their interaction. 3,4) The Hoechst 33258 is bound in the minor groove, with the planar benzimidazole groups oriented parallel to the groove direction and each inner-facing nitrogen atom hydrogen bonding in a bifurcated manner to a pair of adjacent hydrogen bond donors on the edge of the AT base pairs of DNA.…”

mentioning

confidence: 99%

Synthesis, DNA-Binding Activity and Cytotoxicity of Carbamate Derivatives of Hoechst 33258 in Breast Cancer MCF-7 Cells.

Bielawski

Bielawska

Wołczyński

2002

Biological & Pharmaceutical Bulletin

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A series of carbamate derivatives of Hoechst 33258 was prepared as potential anticancer agents. These new compounds (1-4) were readily prepared in good yields by addition of chloroethyl, bromoethyl, chloropropyl or 4-(chloromethyl)phenyl isocyanates to Hoechst 33258. Their cytotoxic activity was evaluated on human breast cancer MCF-7. Compounds 1-4 were more cytotoxic than Hoechst 33258. In particular derivative 4, the most active of the series, is up to 3 times more potent than Hoechst 33258. The DNA-binding ability of these compounds was evaluated by an ultrafiltration method using calf thymus DNA. These data show that in broad terms the cytotoxic potency of 1-4 in cultured breast cancer MCF-7 cells increases, in accord with their increases in DNA affinity, as shown by the binding constant values.

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confidence: 99%

Synthesis, DNA-Binding Activity and Cytotoxicity of Carbamate Derivatives of Hoechst 33258 in Breast Cancer MCF-7 Cells.

Bielawski

Bielawska

Wołczyński

2002

Biological & Pharmaceutical Bulletin

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“…To explore FDLD further, we considered 2 well‐known groove binding DNA ligands, Hoechst 33258 and DAPI, whose LD s are well established . The binding constants of these 2 ligands are both high so we can assume all dye added binds in our experiments.…”

Section: Resultsmentioning

confidence: 99%

Fluorescence detected linear dichroism spectroscopy: A selective and sensitive probe for fluorophores in flow‐oriented systems

et al. 2018

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Fluorescence detection typically enhances sensitivity and selectivity for fluorescent analytes. The potential for combining fluorescence detection with flow orientation of the sample in the normal configuration of linear dichroism experiments is explored in this work by measuring the fluorescence emitted from flow-orientated DNA-bound ligands and M13 bacteriophage. Data for ethidium bromide, Hoechst 33258, and 4,6-diamidino-2-phenyindole are presented. The theoretical basis of the technique is also presented for instruments running in both the fixed direct-current mode, which is the normal operation mode of circular dichroism spectropolarimeters, and also in fixed high-tension voltage mode. The role of the stray light reaching the detector that results in a spectral shape in fixed direct current mode that resembles the shape of a linear dichroism spectrum, rather than the expected reduced linear dichroism, is also explored.

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“…The CD of the norfloxacin–poly[d(G–C) 2 ] complex in this wavelength region contradicts reported results [8], in which these CD of poly[d(G–C) 2 ] was probably over estimated. These weak CD signals suggest that norfloxacin is not a classic minor groove binder, because the classic minor groove binding molecules such as 4′,6‐diamidino‐2‐phenylindole and Hoechst usually exhibit a strong positive band in their drug absorption region [21–23].…”

Section: Resultsmentioning

confidence: 99%

“…6A,B,C), immediately ruling out the possibility of the classic minor groove binding mode, which was observed for 4′,6‐diamidino‐2‐phenylindole and Hoechst. If norfloxacin were bound in the minor groove, the electric transition moments of the drug must be 45°, resulting in the positive LD signal in the drug absorption region (above 300 nm) [21–23]. A strong decrease in the LD magnitude in the DNA absorption region was observed with poly[d(G–C) 2 ] with increasing drug concentration: this decrease is much less significant with poly[d(I–C) 2 ] and poly[d(A–T) 2 ]( Fig.…”

Section: Resultsmentioning

confidence: 99%

Amine group of guanine enhances the binding of norfloxacin antibiotics to DNA

Lee

Yeo

Cho

et al. 2000

European Journal of Biochemistry

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The binding mode of norfloxacin, a quinolone antibacterial agent, in the synthetic polynucleotides poly[d(G±C) 2 ], poly[d(I±C) 2 ] and poly[d(A±T) 2 ] was studied using polarized light spectroscopy, fluorescence spectroscopy and melting profiles. The absorption, circular and linear dichroism properties of norfloxacin are essentially the same for all the complexes, and the angle of electric transition dipole moment I and II of norfloxacin relative to the DNA helix axis is measured as 68±758 for all complexes. These similarities indicate that the binding mode of norfloxacin is similar for all the polynucleotides. The decrease in the linear dichroism (LD) magnitude at 260 nm upon binding norfloxacin, which is strongest for the norfloxacin-poly[d (G±C) . As the amine group of the guanine base protrudes to the minor groove, this result strongly suggests that norfloxacin binds in the minor groove of B-form DNA in a nonclassic manner.Keywords: DNA; fluorescence spectroscopy; norfloxacin; polarized spectroscopy; quinolone.Quinolones are a group of well known synthetic antibiotics. A large amount of biological data indicates that the functional target of these drugs is DNA gyrase, an essential type II DNA topoisomerase that catalyzes the conversion of relaxed supercoiled DNA into a negatively supercoiled form [1]. However, it was reported that norfloxacin ( Fig. 1), one of the most potent DNA gyrase inhibitors of the quinolone family, does not directly bind to gyrase but forms a complex with DNA itself [2]. Following this observation, norfloxacin was observed binding to supercoiled, relaxed, and double and single-stranded DNAs by equilibrium dialysis, membrane ultrafiltration and spectroscopic methods [2±12].Few binding modes of norfloxacin with various DNA have been reported. A cooperative quinolone±DNA binding model for the inhibition of DNA gyrase was proposed [3]. In this model, the bound gyrase induces a binding site for the drug in the relaxed DNA, which is a four-base single-stranded segment. Four drug molecules then assemble inside the single-stranded pocket through hydrogen bonds between the carbonyl group on the quinolone rings and the DNA bases on the separated DNA strands. The drugs interact via stacking of two adjacent quinolone rings and tail-to-tail hydrophobic interactions between the drug molecules. Another binding mode, in which the Mg 21 ion acts as a bridge between the phosphate groups of nucleic acids and the carbonyl and carboxyl moiety of norfloxacin, has been proposed [4]. This model is based on the observations that norfloxacin binds to plasmid DNA in the presence of an appropriate amount of Mg 21 but exhibits no interaction in either an absence or excess of Mg 21 ions in studies using fluorescence spectroscopy, electrophoretic DNA unwinding, and affinity chromatography. Spectroscopic studies for norfloxacin in complex with calf thymus DNA and synthetic polynucleotide reported that the binding mode of norfloxacin deviated from the classic intercalation, although the molecular plane of the norfl...

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DNA structural features responsible for sequence-dependent binding geometries of Hoechst 33258

Cited by 42 publications

References 33 publications

Synthesis, DNA-Binding Activity and Cytotoxicity of Carbamate Derivatives of Hoechst 33258 in Breast Cancer MCF-7 Cells.

Synthesis, DNA-Binding Activity and Cytotoxicity of Carbamate Derivatives of Hoechst 33258 in Breast Cancer MCF-7 Cells.

Fluorescence detected linear dichroism spectroscopy: A selective and sensitive probe for fluorophores in flow‐oriented systems

Amine group of guanine enhances the binding of norfloxacin antibiotics to DNA

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