| 1. |
- Behravan, G., et al.
(författare)
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THE INTERACTION OF ELLIPTICINE DERIVATIVES WITH NUCLEIC-ACIDS STUDIED BY OPTICAL AND H-1-NMR SPECTROSCOPY - EFFECT OF SIZE OF THE HETEROCYCLIC RING
- 1994
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Ingår i: Biopolymers. - : Wiley. - 0006-3525 .- 1097-0282. ; 34:5, s. 599-609
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Tidskriftsartikel (refereegranskat)abstract
- The DNA interaction of derivatives of ellipticine with heterocyclic ring systems with three, four, or five rings and a dimethylaminoethyl side chain was studied. Optical spectroscopy of drug complexes with calf thymus DNA, poly [(dA-dT).(dA-dT)], or poly [(dG-dC).(dG-dC)] showed a 10 nm bathochromic shift of the light absorption bands of the pentacyclic and tetracyclic compounds upon binding to the nucleic acids, which indicates binding by intercalation. For the tricyclic compound a smaller shift of 1-3 nm was observed upon binding to the nucleic acids. Flow linear dichroism studies show that the geometry of all complexes is consistent with intercalation of the ring system, except for the DNA and poly [(dG-dC).(dG-dC)] complexes of the tricyclic compound, where the average angle between the drug molecular plane and the DNA helix axis was found to be 65 degrees. One-dimensional H-1-nmr spectroscopy was used to study complexes between d(CGCGATCGCG)(2) and the tricyclic and pentacyclic compounds. The results on the pentacyclic compound show nonselective broadening due to intermediate chemical exchange of most oligonucleotide resonances upon drug binding. The imino proton resonances are in slow chemical exchange, and new resonances with upheld shifts approaching 1 ppm appear upon drug binding, which supports intercalative binding of the pentacyclic compound. The results on the tricyclic compound show more rapid binding kinetics and very selective broadening of resonances. The data suggest that the tricyclic compound is in an equilibrium between intercalation and minor groove binding, with a preference to bind close to the AT base pairs with the side chain residing in the minor groove. (C) 1994 John Wiley and Sons, Inc.
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| 2. |
- Moon, J. H., et al.
(författare)
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DNA structural features responsible for sequence-dependent binding geometries of Hoechst 33258
- 1996
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Ingår i: Biopolymers. - 0006-3525 .- 1097-0282. ; 38:5, s. 593-606
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Tidskriftsartikel (refereegranskat)abstract
- The complexes of Hoechst 33258 with poly[d(A-T)(2)], poly[d(I-C)(2)], poly[d(G-C)(2)], and poly[d(G-m(5)C)(2)] were studied using linear dichroism, CD, and fluorescence spectroscopies. The Hoechst-poly[d(I-C)(2)] complex, in which there is no quanine amino group protruding in the minor groove, exhibit spectroscopic properties that are very similar to those of the Hoechst-poly[d(A-T)(2)] complex. When bound to both of these polynucleotides, Hoechst exhibits an average orientation angle of near 45 degrees relative to the DNA helix axis for the long-axis polarized low-energy transition, a relatively strong positive induced CD, and a strong increase in fluorescence intensity-leading us to conclude that this molecule also binds in the minor groove of poly[d(I-C)(2)]. By contrast, when bound to poly[d(G-C)(2)], Hoechst shows a distinctively different behavior. The strongly negative reduced linear dichroism in the ligand absorption region is consistent with a model in which part of the Hoechst chromophore is intercalculated between DNA bases. From the low drug:base ratio onset of excitonic effects in the CD and fluorescence emission spectra, it is inferred that another part of the Hoechst molecule may sit in the major groove of poly[d(G-C)(2)] and poly[d(G-m(5)C)(2)] and preferentially stacks into dimers, though this tendency is strongly reduced for the latter polynucleotide. Based on these results, the importance of the interactions of Hoechst with the exocyclic amino group of guanine and the methyl group of cytosine in determining the binding modes are discussed.
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| 3. |
- Sehlstedt, Ulrika, et al.
(författare)
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BINDING OF 4',6-DIAMIDINO-2-PHENYLINDOLE TO POLY(DI-DC) 2 AND POLY(DG-DC) 2 - THE EXOCYCLIC AMINO GROUP OF GUANINE PREVENTS MINOR-GROOVE BINDING
- 1993
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 115:26, s. 12258-12263
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Tidskriftsartikel (refereegranskat)abstract
- Complexes of 4',6-diamidino-2-phenylindole (DAPI) with [poly(dG-dC)]2 and [poly(dI-dC)]2 were studied by optical spectroscopic techniques including linear dichroism (LD), circular dichroism (CD), and fluorescence measurements. The aim was to investigate the importance of the exocyclic amino group of guanine that protrudes into the minor groove of [poly(dG-dC)]2 but is absent in [poly(dI-dC)]2. When bound to [poly(dG-dC)]2, DAPI exhibits a negative, and strongly wavelength-dependent, reduced linear dichroism (LDr) in the DAPI absorption region, a weak positive CD, and a fluorescence behavior that is similar to that of free DAPI with accessibility to quenching by the aqueous solvent. These spectroscopic properties have been interpreted in terms of a major-groove binding geometry by Kim et al. (Kim, S. K.; Eriksson, S.; Kubista, M.; Norden, B. J. Am. Chem. Soc. 1993,115,3441-3447). By contrast, when bound to [poly(dI-dC)]2, DAPI exhibits a strong positive CD in the 300-420-nm region, a positive (wavelength-independent) LD(r), a strong increase of the fluorescence intensity, and shielding to added quencher. These spectroscopic properties closely resemble those of the DAPI-[poly(dA-dT)]2 complex, in which DAPI is situated deep in the minor groove of the polynucleotide. We conclude that the major groove binding geometry of DAPI when complexed with [poly(dG-dC)]2 is a result of a decreased affinity to the minor groove of [poly(dG-dC)]2 due to steric hindrance and decreased electronegative attraction caused by the amino group of guanine.
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| 4. |
- Sehlstedt, Ulrika, et al.
(författare)
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Interaction of Cationic Porphyrins with DNA
- 1994
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 33:2, s. 417-426
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Tuite, Eimer, 1966, et al.
(författare)
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Effects of minor and major groove-binding drugs and intercalators on the DNA association of minor groove-binding proteins RecA and deoxyribonuclease I detected by flow linear dichroism
- 1997
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Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 243:1-2, s. 482-492
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Tidskriftsartikel (refereegranskat)abstract
- Linear and circular dichroic spectroscopies have been employed to investigate the effects of small DNA ligands on the interactions of two proteins which bind to the minor groove of DNA, viz. RecA protein from Escherichia coli and deoxyribonuclease I (bovine pancreas). Ligands representing three specific non-covalent binding modes were investigated: 4',6-diamidino-2-phenylindole and distamycin A (minor groove binders), methyl green (major groove binder), and methylene blue, ethidium bromide and ethidium dimer (intercalators). Linear dichroism was demonstrated to be an excellent detector, in real time, of DNA double-strand cleavage by deoxyribonuclease I. Ligands bound in all three modes interfered with the deoxyribonuclease I digestion of dsDNA, although the level of interference varied in a manner which could be related to the ligand binding site, the ligand charge appearing to be less important. In particular, the retardation of deoxyribonuclease I cleavage by the major groove binder methyl green demonstrates that accessibility to the minor groove can be affected by occupancy of the opposite groove. Binding of all three types of ligand also had marked effects on the interaction of RecA with dsDNA in the presence of non-hydrolyzable cofactor adenosine 5'-O-3-thiotriphosphate, decreasing the association rate to varying extents but with the strongest effects from ligands having some minor groove occupancy. Finally, each ligand was displaced from its DNA binding site upon completion of RecA association, again demonstrating that modification of either groove can affect the properties and behaviour of the other. The conclusions are discussed against the background of previous work on the use of small DNA ligands to probe DNA-protein interactions.
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