Minor‐groove binders are inhibitors of the catalytic activity of DNA gyrases

Störl, K.; Störl, J.; Zimmer, Ch.; Lown, J. William

doi:10.1016/0014-5793(93)81513-y

Cited by 38 publications

(24 citation statements)

References 34 publications

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“…It has been shown that minor groove binding drugs may inhibit eukaryotic topoisomerase II (72)(73)(74) and gyrase (75) to a different extent, depending on the ligand structure.lt is quite possible that the effects of minor groove binders on DNA supercoiling play a role in their inhibitory potency on topoisomerase action, which was not recognized in previous studies on the enzymes (72)(73)(74)(75).…”

Section: Various Minor Groove Binders Affect Dna Superhelicity To a Dmentioning

confidence: 96%

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: Various Minor Groove Binders Affect Dna Superhelicity To a Dmentioning

confidence: 96%

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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“…2 demonstrates that in the presence of 1.5 #g/ml CQ, Nt-lm3 and SN-6999 produce downward shifts (CQ in panels A and B, lanes 7-10). Samples were electrophoresed in 1% agarose gels in 50 mM Trisacetate (pH 8.0), 20 mM sodium acetate, 2 mM EDTA, 18 mM NaCl at 30 V/cm for 18 h. Staining of the DNA in EB (0.5 #g/ml), photography and scanning of negatives have been described previously [3]. Gels with CQ contained CQ at concentrations of 1.5 #g/ml or 3 #g/ml in both the gel and the electrophoresis buffer.…”

Section: Enzymesmentioning

confidence: 99%

“…Drug-induced effects on DNA play a role with respect to their interference with enzymes of DNA metabolism, such as topoisomerases [1][2][3]. Binding of small intercalative ligands, such as EB or CQ, to a topoisomer unwinds DNA as a consequence of intercalation and, upon increasing ligand concentration, alter the superhelix density from negatively supercoiled, via the relaxed, to the positive supercoiled state.…”

Section: Introductionmentioning

confidence: 99%

Studies on the ability of minor groove binders to induce supercoiling in DNA

et al. 1993

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The effect of various non-intercalating minor groove binders on closed circular DNA in the presence of topoisomerase I has been studied by means of agarose gel electrophoresis. Analogues of the netropsin series (lexitropsins) and SN-6999 can effectively produce positive supercoils, as indicated by analysis of the topoisomers in the presence of chloroquine and the evaluated linking number changes. Analogues of the distamycin series are less effective, and bisquaternary ammonium heterocycles, as well as DAPI and pentamidine, were found to be ineffective ligands. The large differences observed in the ability of minor groove binders to induce positive supercoils are discussed.Minor groove binder; Plasmid DNA; Supercoiling

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“…Hence it contributes to the study of DNA base–specific interactions. This antibiotic exerts its biological activity by interfering with proteins that regulate replication and transcription processes [3–5].…”

mentioning

confidence: 99%

Netropsin interactions in the minor groove of d(GGCCAATTGG) studied by a combination of resolution enhancement and ab initio calculations

et al. 2005

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The structure of the complex between the minor groove binder netropsin and d(GGCCAATTGG) was determined via single‐crystal X‐ray techniques. The structure was refined to completion using refmac5.1.24, resulting in a residual R‐factor of 20.0% (including 68 water molecules). Using crystal engineering and cryocooling techniques, the resolution could be enhanced to 1.75 Å, resulting in an unambiguous determination of the drug conformation and orientation. As previously noticed, bifurcated hydrogen bonds are formed between the amide nitrogen atoms of the drug and the N3 and O2 atoms of A and T base pairs, respectively, clearly cataloging the structure to class I. As the bulky NH2 group on guanine was believed to prevent binding of the drug in the minor groove, the detailed nature of several of the amidinium and guanidinium end contacts were further investigated by ab initio quantum chemical methods.

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Minor‐groove binders are inhibitors of the catalytic activity of DNA gyrases

Cited by 38 publications

References 34 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

Studies on the ability of minor groove binders to induce supercoiling in DNA

Netropsin interactions in the minor groove of d(GGCCAATTGG) studied by a combination of resolution enhancement and ab initio calculations

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