| 1. |
- 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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| 2. |
- Carlsson, Christina, 1968, et al.
(författare)
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Screening for genetic mutations
- 1996
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 380:6571, s. 207-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Lincoln, Per, 1958, et al.
(författare)
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CONFORMATION OF THIOCOLCHICINE AND 2 B-RING-MODIFIED ANALOGS BOUND TO TUBULIN STUDIED WITH OPTICAL SPECTROSCOPY
- 1991
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 30:5, s. 1179-1187
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of tubulin with thiocolchicine and two thiocolchicine analogues, one lacking the B ring and one with a six-membered B ring, has been studied by using near-UV and CD spectroscopies. Rapid, reversible binding of the latter analogue to tubulin demonstrates the ability of the colchicine binding site to accommodate the phenyltropone system with a more coplanar conformation than is present in free colchicine. There is no evidence, however, that bound thiocolchicine should have a much less twisted conformation than free thiocolchicine. Thiocolchicine and the bicyclic analogue appear to have approximately the same conformation of the phenyltropone system, in both the free and the bound states, suggesting that this conformation has an optimal arrangement of the phenyl and tropone rings for binding to tubulin. In contrast to colchicine and related derivatives, the three thiocolchicine analogues show pronounced near-UV CD bands upon association to tubulin. No simple relation could be found between the sign pattern of the CD components in the near-UV band of the thiocolchicinoid chromophore and its axial chirality.
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| 4. |
- 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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| 5. |
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| 6. |
- Galt, Sheila, 1956, et al.
(författare)
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EXPERIMENTAL SEARCH FOR COMBINED AC AND DC MAGNETIC-FIELD EFFECTS ON ION CHANNELS
- 1993
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Ingår i: Bioelectromagnetics. - : Wiley. - 1521-186X .- 0197-8462. ; 14:4, s. 315-327
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Tidskriftsartikel (refereegranskat)abstract
- The hypothesis that specific combinations of DC and low frequency AC magnetic fields at so-called cyclotron-resonance conditions could affect the transport of ions through ion channels, or alter the kinetics of ion channels (opening and closing rates), has been tested. As a model system, the ion channels formed by gramicidin A incorporated in lipid bilayer membranes were studied. No significant changes in channel conductance, average lifetime, or formation rate as a function of applied fields could be detected over a wide range of frequencies and field strengths. Experiments were carried out to measure the time-resolved single-channel events and the average conductances of many-channel events in the presence of K+ and H+ ions. The channel blocking effect of Ca++ was also studied. (C) 1993 Wiley-Liss, Inc.
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| 7. |
- Gawronski, J., et al.
(författare)
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Excited States of the Phthalimide Chromophore and Their Exciton Couplings: A Tool for Stereochemical Assignments
- 1998
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 120:46, s. 12083-12091
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Tidskriftsartikel (refereegranskat)abstract
- The electronically excited states of the phthalimide chromophore have been studied by means of linear dichroism (LD) of samples partially oriented in poly(vinyl alcohol) films, magnetic circular dichroism (MCD), and circular dichroism (CD) spectroscopy. On the basis of the LD measurements, the low-energy tail (340-320 nm) of the first absorption band is assigned to an out-of-plane polarized pi-->pi* transition (I). At higher energy, the electronic spectrum is resolved into contributions from five pi-->pi* transitions: II(300 nm, long-axis polarized), III (275 nm, short-axis polarized), IV (235 nm, short-axis polarized), V (220 nm, long-axis polarized), and VI (similar to 210 nm, short-axis polarized). The results from semiempirical (INDO/S-CI) and ab initio (CIS/6-31+G(d)) MO calculations compare well with the proposed assignments of the excited states. Degenerate exciton interaction between electric-dipole-allowed transitions of two phthalimide chromophores is observed in the electronic absorption spectra of the achiral bis-phthalimides 2a-c and in the CD spectrum of the chiral bis-phthalimide 3a. For the latter compound, the solid-state geometry has been determined by X-ray diffraction analysis. Good agreement between experimental and computed CD spectra confirms that the coupled-oscillator exciton model provides the basis for a reliable nonempirical method for the assignment of absolute configuration for this class of compounds. Nondegenerate exciton coupling between phthalimide and benzoate or phenyl chromophores is born out in the CD spectra of homochiral molecules 3c and 3d with the rigid cyclohexane skeleton. Finally, the exciton coupling method is used to make stereochemical assignments for the acyclic, conformationally flexible derivatives 4a-c and 5b.
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| 8. |
- Haaima, G., et al.
(författare)
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Peptide nucleic acids (PNA) derived from N-(N-methylaminoethyl)glycine. Synthesis, hybridization and structural properties
- 1999
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Ingår i: New Journal of Chemistry. - 1369-9261 .- 1144-0546. ; 23:8, s. 833-840
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Tidskriftsartikel (refereegranskat)abstract
- Backbone N-methylated peptide nucleic acids (PNAs) containing the four nucleobases adenine, cytosine, guanine and thymine were synthesized via solid phase peptide oligomerization. The oligomers bind to their complementary target with a thermal stability that is 1.5-4.5 degrees C lower per "N-methyl nucleobase unit" [dependent on the number and position(s) of the N-methyl] than that of unmodified PNA. However, even fully N-methyl modified PNAs bind as efficiently to DNA or RNA targets as DNA itself. Furthermore, the hybridization efficiency per N-methyl unit in a PNA decreased with increasing N-methyl content, and the effect was more pronounced when the N-methyl backbone units are present in the Hoogsteen versus the Watson-Crick strand in (PNA)(2)-DNA triplexes. Interestingly, CD spectral analyses indicate that 30% (3 out of ten) substitution with N-methyl nucleobases did not alter the structure of PNA-DNA (or RNA) duplexes or (PNA)(2)-DNA triplexes, and likewise CD spectroscopy and X-ray crystallography showed no major structural differences between N-methylated (30%) and unmodified PNA-PNA duplexes. However, PNA-DNA duplexes as well as triplexes adopted a different conformation when formed with all-Ai-methyl PNAs.
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| 9. |
- Haq, I., et al.
(författare)
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Interaction of Delta- and Lambda-[Ru(phen)2DPPZ]2+ with DNA: A Calorimetric and Equilibrium Binding Study
- 1995
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 117:17, s. 4788-4796
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence and absorption spectroscopy, isothermal titration calorimetry, and viscosity measurements have been used to characterize the interaction of Delta and Lambda [Ru(phen)(2)DPPZ](2+) with calf thymus DNA. The method of continuous variations revealed two distinct binding stoichiometries for both Delta- and Lambda-DPPZ, corresponding to 0.7 and 3 mol of base pair/mol of ligand. Binding isotherms were obtained for the two enantiomers, both of which show strong binding to DNA, with K = 3.2 x 10(6) M(-1) bp and 1.7 x 10(6) M(-1) bp for the Delta and Lambda isomers, respectively, at 25 degrees C in solutions containing 50 mM NaCl. Titration calorimetry gave Delta H values of +0.3 kcal mol(-1) for Delta-DPPZ and +2.9 kcal mol(-1) for Lambda-DPPZ for their interaction with DNA. These small positive enthalpies, which were confirmed using thermal difference spectroscopy, indicated that the binding of these compounds to DNA is entropically driven. An enthalpy of +2.5 kcal mol(-1) was obtained for the binding of the parent compound, tris(phenanthroline)-Ru(II), to DNA. Titration of all three compounds into buffer gave a nonnegligible heat of dilution. The salt dependence of the binding constant was examined for both isomers. The slope SK = (delta logK/delta log[Na+]) was found to be 1.9 and 2.1 for the Delta and Lambda isomers, respectively. By using polyelectrolyte theory to interpret the observed salt dependence of the equilibrium constant, it can be shown that there is a significant nonelectrostatic contribution to the binding constant. Relative viscosity experiments showed that both Delta- and Lambda-DPPZ increase the length of rod-like DNA, in a manner consistent with binding by classical intercalation. Fluorescence energy transfer experiments provided additional evidence for the intercalation of Delta- and Lambda-[Ru(phen)(2)DPPZ](2+) into DNA.
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| 10. |
- Hsu, D. S., et al.
(författare)
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FLOW LINEAR DICHROISM AND ELECTRON-MICROSCOPIC ANALYSIS OF PROTEIN-DNA COMPLEXES OF A MUTANT UVRB PROTEIN THAT BINDS TO BUT CANNOT KINK DNA
- 1994
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 241:5, s. 645-650
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Tidskriftsartikel (refereegranskat)abstract
- (A)BC excinuclease of Escherichia coli is the enzymatic activity resulting from sequential and partially overlapping actions of UvrA, UvrB, and UvrC protein. UvrA is a molecular matchmaker which promotes the formation of a stable UvrB-damaged DNA complex in which the DNA is kinked by about 130 degrees. The UvrB-DNA complex is then recognized by UvrC) and two incisions are made in the DNA by the joint actions of UvrC and UvrB. A mutant of UvrB (D478A) can be loaded onto the DNA but it does not interact with UvrC to cause a nick 3' to the lesion. Based on the lack of a DNase-I-hypersensitive site in the footprint of the mutant, it was proposed that the lack of incision was due to the inability of the mutant UvrB to kink the DNA. In the current study we have investigated the interaction of the mutant UvrB with DNA using two biophysical methods, flow linear dichroism and electron microscopy. Both methods reveal that the mutant UvrB is unable to bend DNA.
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| 11. |
- Kim, H. K., et al.
(författare)
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Interactions of intercalative and minor groove binding ligands with triplex poly(dA)•[poly(dT)]2and with duplex poly(dA)•poly(dT) and poly[d(A-T)]2studied by CD, LD, and normal absorption
- 1996
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 1520-4995 .- 0006-2960. ; 35:4, s. 1187-1194
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Tidskriftsartikel (refereegranskat)abstract
- The binding of 9-aminoacridine and one bis-acridine compound to double helical poly(dA). poly(dT) and poly[d(A-T)](2) and triple helical poly(dA).[poly(dT)](2) has been investigated using linear dichroism (LD) and circular dichroism (CD). A close examination of the negative reduced LD and the induced CD for the first pi --> pi* transition absorption region leads us to conclude that the acridine moiety of the 9-aminoacridine and bis-acridine molecule intercalates with both duplex and tripler DNA. Binding geometries of the acridine moieties in the examined polynucleotides are similar to those found for the ligands with DNA (Hansen et al. (1984) J. Chem. Sec., Chern. Commun., 509-511). It is also found that both 9-aminoacridine and bis-acridine effectively enhance the thermal stability of the tripler DNA. The corresponding spectra for the complexes of the minor groove binders DAPI and Hoechst with poly(dA).[poly(dT)](2) were studied for comparison. They both show a positive LD and a mixing ratio dependent positive CD in the ligand absorption region, similar to those of their duplex complexes. This indicates that these ligands bind in the grooves of the tripler, probably to the one corresponding to the minor groove of the template duplex.
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| 12. |
- Kim, S.K., et al.
(författare)
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Binding Geometries of Triple Helix Selective Benzopyrido [4,3-b]indole Ligands Complexed with Double- and Triple-Helical Polynucleotides
- 1997
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Ingår i: Biopolymers. - 0006-3525 .- 1097-0282. ; 42:1, s. 101-111
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Tidskriftsartikel (refereegranskat)abstract
- The binding modes of three benzopyrido[4,3-b]indole derivatives (and one benzo[f]pyrido[4-3b]quinoxaline derivative) with respect to double helical poly(dA) . poly(dT) and poly[d(A-T)](2) and triple-helical poly(dA) . 2poly(dT) have been investigated using linear dichroism (LD) and CD: (I) 3-methoxy-11-amino-BePI where BePI = {7H-8-methyl-benzo[e]pyrido[4,3-b]indole}, (II) 3-methoxy-11-[(3'-amino)propylamino]-BePI, (III) 3-methoxy-7-[(3'diethylamino)propylamino]BgPI where BgPI = {benzo[g]pyrido[4,3-b]indole}, and (IV) 3-methoxy-11-[(3'amino)propylamino]BfPQ where BfPQ = {benzo[f]pyrido[4-3b]quinoxaline}. The magnitudes of the reduced LD of the electronic transitions of the polynucleotide bases and of the bound ligands are generally very similar, suggesting an orientation of the plane of the ligands' fused-ring systems preferentially perpendicular to the helix axis. The LD results suggest that all of the ligands are intercalated for all three polynucleotides. The induced CD spectrum of the BePI chromophore in the (II-BePI)-poly[d(A-T)](2) complex is almost a mirror image of that for the (I-BePI)-poly(dA) . poly(dT) and (I-BePI)-poly(dA) . 2poly(dT) complexes, suggesting an antisymmetric orientation of the BePI moiety upon intercalation in poly[d(A-T)]2 compared to the other polynucleotides. The induced CD of I-BePI bound to poly(dA) . 2poly(dT) suggests a geometry that is intermediate between that of its other two complexes. The concluded intercalative binding as well as the conformational variations between the different BePI complexes are of interest in relation to the fact that BePI derivatives are triplex stabilizers.
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| 13. |
- Koch, T., et al.
(författare)
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PNA-Peptide Chimerae
- 1995
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Ingår i: Tetrahedron Letters. - 0040-4039 .- 1873-3581. ; 36:38, s. 6933-6936
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Tidskriftsartikel (refereegranskat)abstract
- Radioactive labelling of PNA has been performed try linking a peptide segment to the PNA which is substrate for protein kinase A. The enzymatic phosphorylation proceeds in almost quantitative yields.
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| 14. |
- 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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| 15. |
- Sehlstedt, U., et al.
(författare)
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Interactions of the Antiviral Quinoxaline Derivative 9-OH-B220 {2,3-dimethyl-6-(dimethylaminoethyl)-9-hydroxy-6H-indolo-[2,3-b] quinoxaline} with Duplex and Triplex forms of Synthetic DNA and RNA
- 1998
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Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 278:1, s. 31-56
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Tidskriftsartikel (refereegranskat)abstract
- The binding of an antiviral quinoxaline derivative, 2,3-dimethyl-6-(dimethylaminoethyl)-9 -hydroxy-6H-indolo-[2,3-b]quinoxaline (9-OH-B220), to synthetic double and triple helical DNA (poly(dA).poly(dT) and poly(dA.)2poly(dT)) and RNA (poly(rA).poly(rU) and poly(rA) .2poly(rU)) has been characterized using flow linear dichroism (LD), circular dichroism (CD), fluorescence spectroscopy, and thermal denaturation. When either of the DNA structures or the RNA duplex serve as host polymers a strongly negative LD is displayed, consistent with intercalation of the chromophoric ring system between the base-pairs/triplets of the nucleic acid structures. Evidence for this geometry also includes weak induced CD signals and strong increments of the fluorescence emission intensities upon binding of the drug to each of these polymer structures. Ln agreement with intercalative binding, 9-OH-B220 is found to effectively enhance the thermal stability of both the double and triple helical states of DNA as well as the RNA duplex. Ln the case of poly(dA).2poly(dT), the drug provides an unusually large stabilization of its triple helical state; upon binding of 9-OH-B220 the tripler-to-duplex equilibrium is shifted towards higher temperature by 52.5 deg. C in a 10 mM sodium cacodylate buffer (pH 7.0) containing 100 mM NaCl and 1 mM EDTA.When triplex RNA serves as host structure, LD indicates that the average orientation angle between the drug chromophore plane and the helix axis of the triple helical RNA is only about 60 to 65 degrees. Moreover, the thermal stabilizing capability, as well as the fluorescence increment, CD inducing power and perturbations of the absorption envelope, of 9-OH-B220 in complex with the RNA tripler are all less pronounced than those observed for the complexes with DNA and duplex RNA. These features indicate binding of 9-OH-B220 in the wide and shallow minor groove of poly(rA).2poly(rU).Based on the present results, some implications for the applications of this low-toxic, antiviral and easily administered drug in an antigene strategy, as well as its potential use as an antiretroviral agent, are discussed
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| 16. |
- Son, G.S., et al.
(författare)
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Binding Mode of Norfloxacin to Calf Thymus DNA
- 1998
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 120:26, s. 6451-6457
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Tidskriftsartikel (refereegranskat)abstract
- Norfloxacin, a quinolone antibacterial reagent, has been studied with respect to its binding to calf thymus DNA using fluorescence and linear dichroism techniques and unwinding of supercoiled DNA. The fluorescence of norfloxacin is strongly quenched in the presence of DNA and using this decrease in a fluorescence titration the equilibrium constant of the complex formation was established to be 2.8 x 10(3) M-1. The electric transition moments of the norfloxacin chromophore have been analyzed using fluorescence anisotropy, magnetic circular dichroism, and linear dichroism in stretched poly(vinyl alcohol) film and INDO/S calculations. These data are then used to interpret flow linear dichroism results for the norfloxacin-DNA complex. The transition moments for the long-wavelength transitions are found to be oriented at about 65.0-85.0 degrees with respect to the DNA helix axis. A near perpendicular orientation of the norfloxacin chromophore plane makes it possible to exclude classical groove or surface binding modes. The possibility of a classical intercalation binding mode also can be ruled out from unwinding experiments. However, it is shown that the molecular plane of norfloxacin is near perpendicular relative to the DNA helix axis with a possibility of a bending of the DNA helix at the binding site.
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| 17. |
- WITTUNG, P, et al.
(författare)
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PHOSPHOLIPID MEMBRANE-PERMEABILITY OF PEPTIDE NUCLEIC-ACID
- 1995
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Ingår i: FEBS LETTERS. - 0014-5793. ; 365:1, s. 27-29
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Tidskriftsartikel (refereegranskat)abstract
- Phospholipid vesicles (liposomes) as membrane models have been used to study the penetration properties of peptide nucleic acid (PNA), a new DNA analog in which the nucleobases are attached to a pseudo-peptide backbone, The liposomes were characterised by
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