DNA Drug Interactions Studied with Polarized Light Spectroscopy: The DAPI Case

Nordén, Bengt; Eriksson, Svante; Kim, S. K.; Kubista, Mikael; Lyng, Reidar; Åkerman, Björn

doi:10.1007/978-94-011-3728-7_2

Cited by 15 publications

(21 citation statements)

References 49 publications

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“…The ability of psoralens to photo- for the 380 nm transition and 74° for the transition at 330 nm (see text) suggests a perpendicular orientation in the major groove or intercalation. Reproduced with permission from Norden et al (19906). Note the drop in LD r above 360 nm in the DNA case for large binding ratios consistent with the occurrence of GC-type binding.…”

Section: Intercalated Drugsmentioning

confidence: 63%

Linear dichroism spectroscopy of nucleic acids

Nordén

Kubista

Kurucsev

1992

Quart. Rev. Biophys.

359

376

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This review will consider solution studies of structure and interactions of DNA and DNA complexes using linear dichroism spectroscopy, with emphasis on the technique of orientation by flow. The theoretical and experimental background to be given may serve, in addition, as a general introduction into the state of the art of linear dichroism spectroscopy, particularly as it is applied to biophysical problems.

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Section: Intercalated Drugsmentioning

confidence: 63%

Linear dichroism spectroscopy of nucleic acids

Nordén

Kubista

Kurucsev

1992

Quart. Rev. Biophys.

359

376

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“…But DAPI differs markedly from the pyrrole-amidine drugs with regard to its capacity to interact with G C sequences. Wilson et al (1989Wilson et al ( ,1990b and Norden et al (1990) have demonstrated that DAPI has the property to intercalate at G C sites. This unusual and extremely interesting behaviour was established on the basis of results from viscometric, NMR, flow linear dichroism, fluorescence, absorption, circular dichroism and kinetic measurements.…”

Section: Minor Groove Bindersmentioning

confidence: 99%

Drug—DNA sequence‐dependent interactions analysed by electric linear dichroism

Bailly

Hénichart

Colson

et al. 1992

J of Molecular Recognition

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The interactions between 20 drugs and a variety of synthetic DNA polymers and natural DNAs were studied by electric linear dichroism (ELD). All compounds tested, including several clinically used antitumour agents, are thought to exert their biological activities mainly by virtue of their abilities to bind to DNA. The selected drugs include intercalating agents with fused and unfused aromatic structures and several groove binders. To examine the role of base composition and base sequence in the binding of these drugs to DNA, ELD experiments were carried out with natural DNAs of widely differing base composition as well as with polynucleotides containing defined alternating and non-alternating repeating sequences, poly(dA).poly(dT), poly(dA-dT).poly(dA-dT),poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC). Among intercalating agents, actinomycin D was found to be by far the most GC-selective. GC selectivity was also observed with an amsacrine-4-carboxamide derivative and to a lesser extent with methylene blue. In contrast, the binding of amsacrine and 9-aminoacridine was practically unaffected by varying the GC content of the DNAs. Ethidium bromide, proflavine, mitoxantrone, daunomycin and an ellipticine derivative were found to bind best to alternating purine-pyrimidine sequences regardless of their nature. ELD measurements provided evidence for non-specific intercalation of amiloride. A significant AT selectivity was observed with hycanthone and lucanthone. The triphenyl methane dye methyl green was found to exhibit positive and negative dichroism signals at AT and GC sites, respectively, showing that the mode of binding of a drug can change markedly with the DNA base composition. Among minor groove binders, the N-methylpyrrole carboxamide-containing antibiotics netropsin and distamycin bound to DNA with very pronounced AT specificity, as expected. More interestingly the dye Hoechst 33258, berenil and a thiazole-containing lexitropsin elicited negative reduced dichroism in the presence of GC-rich DNA which is totally inconsistent with a groove binding process. We postulate that these three drugs share with the trypanocide 4',6-diamidino-2-phenylindole (DAPI) the property of intercalating at GC-rich sites and binding to the minor groove of DNA at other sites. Replacement of guanines by inosines (i.e., removal of the protruding exocyclic C-2 amino group of guanine) restored minor groove binding of DAPI, Hoechst 33258 and berenil. Thus there are several cases where the mode of binding to DNA is directly dependent on the base composition of the polymer. Consequently the ELD technique appears uniquely valuable as a means of investigating the possibility of sequence-dependent recognition of DNA by drugs.

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“…Knowledge of binding geometry is needed if an optical probe is used (approximately a = 90 0 for intercalators, and 45 0 for minor-groove binders, see Norden et al 1990). For B-form fibre DNA (Arnott & Hukins, 1972) a theoretical, effective value of a, corresponding to the DNA base transitions at 260 nm, is 86°, which allows 5 to be determined from the LD measured at this wavelength on unmodified DNA (Matsuoka & Norden, 19826, 1983):…”

Section: Linear Dichroismmentioning

confidence: 99%

“…Of these, EB and AO are intercalators known to alter the length and flexibility of DNA (Berman & Young, 1981). DAPI binds in the minor groove at AT-rich sequences and provides increased stiffness to the DNA chain; in GC regions there is evidence that DAPI may be in part intercalated and here it makes DNA more flexible (Norden et al 1990). Furthermore, all these probes are cations and hence diminish the net negative charge of DNA and the electrophoretic mobility.…”

Section: Fluorescence Microscopymentioning

confidence: 99%

“…EPO is a new way of producing DNA orientation and may be used for studying structure, dynamics and interactions, along the same lines as electric and flow LD have been used to obtain information about DNA complexes with drugs and proteins (see, for example, Schellman & Jensen, 1987;Takahashi et al 1989;Charney, 1988;Norden et al 1990). For example, LD could reveal structural details of the conformational alterations that are indicated through electrophoretic mobility changes of supercoiled DNA upon, for example, covalent modification (Yoshida et al 1987).…”

Section: Future Prospectsmentioning

confidence: 99%

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Microscopic behaviour of DNA during electrophoresis: electrophoretic orientation

Nordén

Elvingson

Jönsson

et al. 1991

Quart. Rev. Biophys.

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The study of the behaviour of DNA when subjected to electric fields poses several intriguing problems of fundamental physico-chemical importance. Electric field (Kerr effect) orientation of DNA in free solution as well as migration of DNA in gel electrophoresis are two well-established, but so far rather separate, research fields. Whereas the first one has been generally concerned with basic structural and dynamical properties of DNA (Charney, 1988), the second is closely related to techniques of molecular biology (for a review on DNA electrophoresis, see stellwagen 1987).

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DNA Drug Interactions Studied with Polarized Light Spectroscopy: The DAPI Case

Cited by 15 publications

References 49 publications

Linear dichroism spectroscopy of nucleic acids

Linear dichroism spectroscopy of nucleic acids

Drug—DNA sequence‐dependent interactions analysed by electric linear dichroism

Microscopic behaviour of DNA during electrophoresis: electrophoretic orientation

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