| 1. |
- Behravan, G., et al.
(author)
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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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In: Biopolymers. - : Wiley. - 0006-3525 .- 1097-0282. ; 34:5, s. 599-609
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Journal article (peer-reviewed)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. |
- Doglia, S. M., et al.
(author)
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QUINACRINE - SPECTROSCOPIC PROPERTIES AND INTERACTIONS WITH POLYNUCLEOTIDES
- 1993
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In: Biopolymers. - : Wiley. - 0006-3525 .- 1097-0282. ; 33:9, s. 1431-1442
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Journal article (peer-reviewed)abstract
- The acridine dye quinacrine and its interactions with calf thymus DNA, poly(dA-dT).poly(dA-dT), and poly(dG-dC).poly(dG-dC) were studied by light absorption, linear dichroism, and fluorescence spectroscopy. The transition moments of quinacrine give rise to absorption bands polarized along the short axis (400-480-nm band), and the long axis (345-nm and 290-nm bands) of the molecule, respectively. Linear dichroism studies show that quinacrine intercalates into calf thymus DNA as well as into the polynucleotides, displaying fairly homogeneous binding to poly (dA-dT).poly(dA-dT), but more than one type of intercalation site for calf thymus DNA and poly(dG-dC).poly(dG-dC). Fluorescence spectroscopy shows that for free quinacrine the pK = 8.1 between the mono- and diprotonated states also remains unchanged in the excited state. Quinacrine bound to calf thymus DNA and polynucleotides exhibits light absorption typical for the intercalated diprotonated form. The fluorescence enhancement of quinacrine bound to poly (dA-dT).poly(dA-dT) may be due to shielding from water interactions involving transient H-bond formation. The fluorescence quenching in poly (dG-dC).poly (dG-dC) may be due to excited state electron transfer from guanine to quinacrine. (C) 1993 John Wiley & Sons, Inc.
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| 3. |
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| 4. |
- Eriksson, M., et al.
(author)
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BINDING OF DELTA- RU(PHEN)(3) (2+) AND LAMBDA- RU(PHEN)(3) (2+) TO D(CGCGATCGCG) (2) STUDIED BY NMR
- 1994
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In: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 33:17, s. 5031-5040
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Journal article (peer-reviewed)abstract
- The interactions of the Delta and Delta enantiomers of the chiral metal complex [Ru(phen)(3)](2+) (phen = 1,10-phenanthroline) with the oligonucleotide duplex [d(CGCGATCGCG)](2) have been studied with NMR and CD spectroscopy. From NOESY data it is shown that the interaction primarily takes place in the minor groove of the oligonucleotide which remains in a B-like conformation. The observed NOEs also provide evidence that the metal complexes preferentially bind to the central AT region. The observed AT specificity is more pronounced with the Delta as compared to the Delta enantiomer, which interacts with a larger part of the oligonucleotide. Furthermore, the NOESY data show that neither of the enantiomers binds by classical intercalation. This is also supported by a comparison study of the analogue [Ru(phen)(2)DPPZ](2+) (DPPZ = dipyrido[ 3,2-a:2',3'-c] phenazine) which intercalates in DNA. The NMR as well as the CD results show that the Delta and Delta enantiomers of [Ru(phen)(3)](2+) bind in different modes to [d(CGCGATCGCG)](2). Comparison of CD spectra of the metal complex in the presence of [d(CGCGATCGCG)](2), poly(dAdT).poly(dAdT), poly(dGdC).poly(dGdC), and calf thymus DNA suggests that these binding modes are independent of DNA sequence. The results are found to be compatible with binding of Delta-[Ru(phen)(3)](2+) by insertion of two phenanthroline ligands into the minor groove, causing minor distortions of the DNA structure, whereas the Delta enantiomer binds in a mode that leaves the DNA structure unaffected.
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| 5. |
- Eriksson, M., et al.
(author)
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LOCATION OF EXCIMER-FORMING ADDUCTS OF (+)-ANTI-BENZO A PYRENE DIOL EPOXIDE IN DNA
- 1993
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In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 115:5, s. 1639-1644
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Journal article (peer-reviewed)abstract
- Covalent adducts of the carcinogenic polycyclic aromatic hydrocarbon (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide ((+)-anti-BPDE) in polynucleotides have been studied by fluorescence spectroscopy. The pyrenyl chromophores of the BPDE adducts, linked by the C10 atom to the exocyclic nitrogen of guanine, interact in the photoexcited state, as evidenced by excimer fluorescence. Strong BPDE excimer fluorescence is observed in the alternating poly(dGdC).poly(dGdC) sequence, whereas it is weak in the homopolymeric poly(dG).poly(dC) and in calf thymus DNA. No excimer fluorescence is observed for the BPDE adducts in poly(dAdC).poly(dGdT) or poly(dAdG).poly(dCdT). It is concluded that the formation of BPDE excimers in polynucleotides requires binding to guanines on different strands on consecutive basepairs. The experimental results are supported by graphics modeling and energy minimization of BPDE adducts in various oligonucleotide sequences. The results show that the most favorable arrangement for excimer formation of the BPDE-dG adducts is in a 5'(dCdG-BPDE).5'(dCdG-BPDE) sequence, where the pyrenyl chromophores interact in the minor groove.
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| 6. |
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| 7. |
- Graslund, A., et al.
(author)
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DYNAMICS OF BENZO A PYRENE DIOL EPOXIDE ADDUCTS IN POLY(DG-DC) . (DG-DC) STUDIED BY SYNCHROTRON EXCITED FLUORESCENCE POLARIZATION ANISOTROPY DECAY
- 1992
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In: Biophysical Chemistry. - : Elsevier BV. - 1873-4200 .- 0301-4622. ; 44:1, s. 21-28
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Journal article (peer-reviewed)abstract
- Time-resolved fluorescence studies have been performed on (+)-anti-7,8-dihydrodiol-9,10-epoxy-benzo[a]pyrene adducts in double-stranded poly(dG-dC) . (dG-dC). Part of the adduct population gives rise to excimer fluorescence. The heterogeneous fluorescence emission decay curves at 22-degrees-C could be resolved into three components with lifetimes: 0.4 ns, 3 ns and 24 ns for the total fluorescence (monomer and excimer emission), and 0.5 ns, 5 ns and 24 ns, respectively, for excimer emission alone. The relative amplitudes for the longer lifetimes were larger for the pure excimer population than for the mixed population. The fluorescence polarization anisotropy decay curves were resolved into two components of rotational correlation times: 0.4 ns and 25 ns for the total fluorescence and 0.3 ns and 33 ns for the excimer fluorescence. We interpret the two rotational correlation times to correspond to local motion of the adduct and segmental motion of the polynucleotide, respectively.
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| 8. |
- Leijon, M., et al.
(author)
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STRUCTURAL CHARACTERIZATION OF PNA-DNA DUPLEXES BY NMR - EVIDENCE FOR DNA IN A B-LIKE CONFORMATION
- 1994
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In: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 33:33, s. 9820-9825
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Journal article (peer-reviewed)abstract
- The nucleic acid analogues PNA (peptide nucleic acids) hybridize with DNA of complementary sequence. The solution structures of two PNA-DNA duplexes, H-(GCTATGTC)-NH2.d(GACATAGC) and H-(GTAGATCACT)-NH2.d(AGTGATCTAC), have been studied by H-1 NMR. It was found that the PNA-DNA hybrids are base paired by hydrogen bonds, most likely of the Watson-Crick type. From two-dimensional NOESY and COSY results it is concluded that the DNA strand in the PNA-DNA complex adopts a B-like structure with the deoxyribose sugars in the C2'-endo conformation.
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| 9. |
- Nordén, Bengt, 1945, et al.
(author)
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DNA INTERACTION WITH CHIRAL METAL-COMPLEXES
- 1991
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In: Nucleosides and Nucleotides. - : Informa UK Limited. - 0732-8311 .- 1532-2335. ; 10:1-3, s. 195-205
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Journal article (peer-reviewed)abstract
- Despite extensive study of DNA interaction with propeller-shaped metal complexes, such as the DELTA and LAMBDA enantiomers of [Ru(1,10-phenanthroline)3]2+, the basis for their enantioselectivity, and even their binding modes, are not yet fully understood. H-1 NMR studies of the interactions with the self-complementary oligonucleotide d(CGCGATCGCG)2 indicate that both enantiomers bind into the minor groove of the central AT-TA region, but with a rapid exchange between the bound and free states. Flow linear dichroism (FLD) and circular dichroism (CD) show different binding geometries for the two enantiomers. These two geometries are found in natural DNA as well as in a number of different B form polynucleotides, virtually independent of base composition and of methylation. The DNA interaction with the [Ru(1,10-phenanthroline)3]2+ complexes will be reconsidered in the light of NMR, FLD, CD and fluorescence results.
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| 10. |
- Ponten, I., et al.
(author)
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SPECTROSCOPIC STUDIES OF THE TRANS ADDUCTS DERIVED FROM (+)-ANTI-BENZO A PYRENE-7,8-DIHYDRODIOL-9,10-EPOXIDE AND (-)-ANTI-BENZO A PYRENE-7,8-DIHYDRODIOL-9,10-EPOXIDE AND THE OLIGONUCLEOTIDE 5'-D(CCTATAGATATCC)
- 1994
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In: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 15:10, s. 2207-2213
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Journal article (peer-reviewed)abstract
- The oligonucleotide 5'-d(CCTATAGATATCC) has been reacted with the (+)- or (-)-enantiomers of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-and (-)-anti-BPDE respectively]. Consistent with previous studies employing single-stranded oligonucleotides, adduct formation of both anti-BPDE enantiomers preferentially involved trans-addition of the C10 position of the diol-epoxide to the exocyclic nitrogen of deoxyguanosine [in the following abbreviated as (+)-BPDE(t)-N-2-G and (-)-BPDE(t)-N-2-G adducts respectively]. The unmodified or (+)-BPDE(t)-N-2-G-modified oligonucleotide was allowed to form duplexes with the complementary sequence 5'-d(GGATATCTATAGG) or sequences in which C has been replaced with T, G or A and analysed with regard to thermal stability. The presence of a (+)-BPDE(t)-N-2-G adduct in oligonucleotide duplexes substantially decreased the value of the melting point relative to the corresponding unmodified duplex. In mismatched complexes containing the (+)-BPDE(t)-N-2-G adduct, a further decrease in thermal stability was observed. The presence of a (+)-BPDE(t)-N-2-G adduct did not seem to change the extent of hyperchromicity (approximate to 20%) upon melting. 5'-d(GGATATCTATAGG) or strands in which C was replaced with T,G or A were gradually added to (+)- or (-)-BPDE(t)-N-2-G-modified oligonucleotides and the fluorescence emission intensity was determined. In all cases with (+)-BPDE(t)-N-2-G, except when C was replaced with A in the complement, the fluorescence intensity steadily decreased and became constant at equal strand concentrations. When a strand containing A in place of C was gradually added to the (+)-BPDE(t)-N-2-G oligonucleotide, a marked increase in the fluorescence intensity was observed (>3-fold). In contrast, addition of strands containing A, T or G to the (-)-BPDE(t)-N-2-G-modified oligonucleotide increased tbe fluorescence intensity from 1.5- to >5-fold. Addition of the fully complementary sequence to the (-)-BPDE(t)-N-2-G-containing oligonucleotide resulted in reduced fluorescence, however less pronounced than with the (+)-BPDE(t)-N-2-G-modified analogue. Significant changes in spectral properties of the adducts were observed in the duplexes. The absorption and fluorescence excitation maxima of the single-stranded (+)-BPDE(t)-N-2-G-modified oligonucleotide were at 353 nm. Insertion of C or A opposite the adduct caused a significant shift of these maxima to shorter wavelengths (347-348 nm). Addition of acrylamide, a fluorescence quencher, reduced the fluorescence intensity in all cases, but to variable extents. The adducts not quenchable by acrylamide demonstrate spectral properties similar to those of the single-stranded (+)-BPDE(t)-N-2-G-modified oligonucleotide.
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