Binding of nonintercalative antitumor drugs to DNA-polymers: structural effects of bisquaternary ammonium heterocycles.

  title={Binding of nonintercalative antitumor drugs to DNA-polymers: structural effects of bisquaternary ammonium heterocycles.},
  author={G{\"u}nther Burckhardt and C. Zimmer and Bruce C. Baguley},
  journal={Journal of biomolecular structure \& dynamics},
  volume={4 5},
The binding of the antitumor agents SN-16814 nd SN-13232 to various DNA's in solution was monitored by CD and UV absorption measurements. In addition comparative studies with dA.dT containing duplex DNA of the related ligands SN-6136 and SN-6324 were included with respect to effects of structural variations. In general all four ligands show a dA.dT preference in their binding affinity to DNA. Differences were observed for the reaction of SN-16814 which contains bicyclic ring system: it has a… 
9 Citations

A Structure-Function Study of Nucleic Acid-Fluorenone Complexes

  • G. BischoffUlrich Gromann S. Hoffmann
  • Chemistry, Biology
    Journal of biomolecular structure & dynamics
  • 2000
Abstract Several 2,7-bis-[(dialkylamino)-acetylamino]-fluoren-9-one derivatives (fluoramides) were synthesized as analogues of the DNA binding compound tilorone

Efficient conjugation and characterization of distamycin-based peptides with selected oligonucleotide stretches.

UV results suggest that the thiazolidine and oxime linkages do not significantly influence the process of distamycin binding to the minor groove surface of the DNA duplex, and reinforce the fact that the specific stabilization of A/T rich DNA-DNA duplexes bydistamycin was preserved upon conjugation with oligonucleotide stretches.

Oligopyridine-ruthenium(II)-amino acid conjugates: synthesis, characterization, DNA binding properties and interactions with the oligonucleotide duplex d(5'-CGCGCG-3')2.

CD and T(m) data indicate that all diastereomeric complexes bind to the DNA major groove, Delta-diastereomers in a similar manner, while Lambda-diastsomers in dependence of the nature of the amino acid.

Sequence Specific Modulation of DNA Restriction Enzyme Cleavage by Minor Groove Binders

The inhibition of the restriction endonuclease PvuII indicates that ligand binding in close vicinity to the cleavage sites is also involved in the enzyme inhibition, and the dAdT-content in proximity to the palindromic sequences of three DraI cutting sites in pUC19 DNA explains why the derivative SN 6053 protects these sequences in different manners.

DNA Binding Properties of Novel Dansylated Distamycin Analogues in Which the Fluorophore is Directly Conjugated to the N-methyl-pyrrole Carboxamide Backbone

Two oligopeptides that bear the dansyl group coupled directly to the N-terminus of the conjugated N-methylpyrrole carboxamide network are developed and ‘reported’ DNA binding in the form of an enhanced fluorescence emission.

DNA binding selectivity of oligopyridine-ruthenium(II)-lysine conjugate.

Circular dichroism studies indicate that the hydrolyzed complex binds to DNA, increasing the unwinding of the DNA helix with an unwinding angle calculated as Φ = 12 ± 2°.

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.

The DNA binding selectivity of three ligands of a series of antitumor agents of bisquaternary ammonium heterocycles has been investigated by means of CD spectroscopy and melting measurements and it is concluded that the agents SN-6132,SN-6131 and SN- 6113 have relatively high affinity to AT base pair sequences whereas the binding to GC pairs is very low.



Existence of an extended series of antitumor compounds which bind to deoxyribonucleic acid by nonintercalative means.

Viscometric titrations of bacteriophage PM2 closed circular DNA, in addition to spectrophotometric and fluorometric methods, were used to investigate the mode of DNA binding of a number of antitrypanosomal and antitumor compounds, and it is proposed that the compounds all bind in the minor groove of the DNA double helix.

Binding of CC‐1065 to poly‐ and oligonucleotides

The binding of the antitumor agent CC‐1065 to a variety of poly‐ and oligonucleotides was studied by electronic absorption, CD, and resistance to removal by Sephadex column chromatography and results of x‐ray studies suggest that A‐form triplex DNA retains some structural features of B‐form DNA that are not present in A‐ form duplex DNA.

Conformation dependent binding of netropsin and distamycin to DNA and DNA model polymers.

The binding of the antibiotics netropsin and distamycin A to DNA has been studied by thermal melting, CD and sedimentation analysis and it is suggested that the binding is stabilized primarily by hydrogen bonding and electrostatic interactions probably in the narrow groove of the DNA helix, but without intercalation.

The molecular origin of DNA-drug specificity in netropsin and distamycin.

The netropsin molecule has an intrinsic twist that favors insertion into the minor groove of B-DNA, and it is given a small additional twist upon binding, which could lead to a class of synthetic "lexitropsins," capable of reading any desired short sequence of DNA base pairs.

Two binding modes of netropsin are involved in the complex formation with poly(dA-dT).poly(dA-dT) and other alternating DNA duplex polymers.

Using CD measurements, it is shown that the interaction of netropsin to poly(dA-dT) involves two binding modes at low ionic strength, which is primarily determined by specific interaction to dA.dT base pairs.

Thermodynamics of drug-DNA interactions.

Thermodynamic parameters are interpreted in terms of specific interactions that have been proposed as part of models for the binding of each drug.

Z‐DNA and other non‐B‐DNA structures are reversed to B‐DNA by interaction with netropsin

  • C. ZimmerChristian MarckWilhelm Guschlbauer
  • Biology, Chemistry
    FEBS letters
  • 1983

Influence of nucleotide sequence on dA.dT-specific binding of Netropsin to double stranded DNA.

It is experimentally shown that the insertion of a dG.dC pair in dA.dT sequences strongly reduces the specific interaction of Nt with DNA duplexes.