DNA Binding of the Nonintercalative Ligands SN-6132, SN-6131 and SN-6113: Minor Variations of the Ligand Structure May Cause Changes in the Base Pair Preference

Luck, G.; Störl, J.; Baguley, Bruce C.; Zimmer, Christoph

doi:10.1080/07391102.1992.10508667

Cited by 8 publications

(4 citation statements)

References 28 publications

(38 reference statements)

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“…Some basic chemical structures of different classes of non-intercalating minor groove binders used in this study are presented in Figure 1. Structures of 1m 3 and bis-Nt-X are given in (13,14), those of hisquaternary ammonium heterocycles in (15)(16)(17). Informations concerning the mode of interaction with DNA and other properties of the ligands are reviewed in (17)(18)(19)(20) Boundary sedimentation experiments were performed by running the An-F rotor with three double-sector cells in a Beckman model Spinco E analytical ultracentrifuge equipped with monochromator and photoelectric scanning system.…”

Section: Drugsmentioning

confidence: 99%

Modulation of DNA Supercoiling by Interaction with Netropsin and Other Minor Groove Binders

Triebel

Walter

Burckhardt

et al. 1994

Journal of Biomolecular Structure and Dynamics

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The assay of DNA unwinding by ethidium, followed by sedimentation velocity techniques, was applied to complexes of supercoiled plasmid DNA with different non-intercalating drugs which strongly and sequence-specifically bind to DNA. Compared with the behaviour of naked DNA, most of the complexes exhibit an increase in the critical EB/nucleotide binding ratio associated with the principal minimum in the sedimentation profile. Using netropsin (Nt) as the paradigm of the minor groove binders investigated, the drug-induced alterations in various structural parameters of both the relaxed and supercoiled form of DNA are described. Whereas winding number, helical repeat (both being defined with reference to a surface normal), and linking number of the superhelical DNA remain constant in our experiments, its twist number, surface twist, number of superhelical turns as well as the absolute values of linking number difference, superhelix density, and writhing number increase on binding of Nt. Correspondingly, compared with the naked relaxed DNA a higher linking number (or twist number, or winding number), a higher average duplex winding angle and a lower helical repeat have to be assigned to the relaxed Nt-DNA complex. The various minor groove binders investigated were found to differ considerably in their efficiency to alter the structure of supercoiled DNA.

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Section: Drugsmentioning

confidence: 99%

Modulation of DNA Supercoiling by Interaction with Netropsin and Other Minor Groove Binders

Triebel

Walter

Burckhardt

et al. 1994

Journal of Biomolecular Structure and Dynamics

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“…Although it is acknowledged that these positive bands outside the polynuc}eotide region appear to reflect the presence of bound ligand molecules [20], this interpretation is not so obvious for mitomycin C, since at the region around 380 nm the drug alone produces a clear c.d. band of relatively large magnitude [5].…”

Section: CD Studiesmentioning

confidence: 99%

Mitomycin C binding to poly[d(G-m5C)]

Portugal

Sánchez‐Baeza

1995

Biochemical Journal

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Poly[d(G-m5C)] was modified by reductively activated mitomycin C, an anti-tumour drug, under buffer conditions which are known to favour either the B or the Z conformations of DNA. C.d. and 31P-n.m.r. were used to characterize the poly[d(G-m5C)]-mitomycin cross-linked complexes, as well as the effects on the equilibrium between the B and Z forms of the polynucleotide. Mitomycin C appears to inhibit the B-->Z transition, even in the presence of 3 mM MgCl2, while the Z-form of poly[d(G-m5C)] does not interact significantly with the drug under bifunctionally activating conditions; thus no reversion from the Z-form to the B-form of the polynucleotide can be observed under the salt conditions which are required for the Z-form to exist.

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“…Materials. DNA samples from calf thymus (CT DNA: 58 mol % AT) and GC-rich DNA from Streptomyces chrysomallus (SC DNA: 28 mol % AT) were purified and used as previously described (14). Synthetic DNA duplex polymers were from Boehringer (Mannheim) and used without further purification.…”

mentioning

confidence: 99%

Binding of 2-Azaanthraquinone Derivatives to DNA and Their Interference with the Activity of DNA Topoisomerases in Vitro

et al. 1998

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We have investigated the binding ability to DNA of compounds belonging to the 2-azaanthraquinone-type structure and have examined the effect on the activity of DNA gyrase as well as on mammalian topoisomerases in vitro. Using different biophysical techniques it was found that one of these ligands, 9-((2-dimethylamino)ethyl)amino)-6-hydroxy-7-methoxy-5, 10-dihydroxybenzo[g]isoquinoline-5,10-dione (TPL-I), is an intercalating DNA binding agent, whereas the parent compound tolypocladin (TPL) and a derivative (TPL-II) showed almost no similar affinity to DNA. CD measurements demonstrated a significant and selective binding tendency of TPL-I to alternating purine/pyrimidine sequences with some preference for poly(dA-dT). poly(dA-dT). Tm values were increased of the ligand complex with the alternating AT-containing duplex polymer. The binding to various DNAs was characterized by CD and visible absorption spectral changes. From the latter, different binding constants of 6.2 x 10(5) and 1.5 x 10(5) M-1 were obtained for poly(dA-dT).poly(dA-dT) and poly(dA). poly(dT), respectively. Sedimentation measurements with supercoiled pBR322 plasmid DNA clearly indicated an intercalative binding mechanism associated with an unwinding angle of about 18 degrees. These results suggest that the intercalative binding of TPL-I is promoted by the 2-(dimethylamino)ethylamino group substituted on carbon 9 of the anthraquinone system. The cytotoxic compound TPL-I, but not TPL or TPL-II, effectively inhibited the DNA supercoiling reaction of DNA gyrase and the activity of mammalian topoisomerases I and II as measured by the relaxation assay. TPL-I affects the cleavage reaction of topoisomerases on a single site located in alternating purine-pyrimidine sequence regions. The inhibitory potency of TPL-I can be ascribed to a blocking of cleavage sites on the DNA substrate, which correlates with the sequence preference of the ligand.

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DNA Binding of the Nonintercalative Ligands SN-6132, SN-6131 and SN-6113: Minor Variations of the Ligand Structure May Cause Changes in the Base Pair Preference

Cited by 8 publications

References 28 publications

Modulation of DNA Supercoiling by Interaction with Netropsin and Other Minor Groove Binders

Modulation of DNA Supercoiling by Interaction with Netropsin and Other Minor Groove Binders

Mitomycin C binding to poly[d(G-m5C)]

Binding of 2-Azaanthraquinone Derivatives to DNA and Their Interference with the Activity of DNA Topoisomerases in Vitro

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