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

• Published in: FEBS letters 1993-11, Vol.334 (1), p.49-54
• Main Authors: Störl, K., Burckhardt, G., Lown, J.W., Zimmer, Ch
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; bis-Nt-x (x = 5,6,8) bifunctional netropsins linked by x methylene residues; CQ, chloroquine; DAPI, 4′,6-diamino-phenylindole; Distamycins - pharmacology; DNA Topoisomerases, Type I - metabolism; DNA, Superhelical - chemistry; Dst-2, analogue of distamycin containing two N-methylpyrrole groups; Dst-3, distamycin A; Dst-lm2, distamycin containing two N-methylimidazole groups; EB, ethidium bromide; Electrophoresis, Agar Gel; General aspects; Medical sciences; Minor groove binder; Netropsin - analogs & derivatives; Netropsin - pharmacology; Nt, netropsin; Nt-lmx, netropsin analogues (lexitropsins) containing two (x = 2) or three (x = 3) N-methylimidazole residues; Nucleic Acid Conformation - drug effects; Pharmacology. Drug treatments; Plasmid DNA; Pyridinium Compounds - pharmacology; Quaternary Ammonium Compounds - pharmacology; Quinolinium Compounds - pharmacology; SN-6999, SN-16841, SN-13282, SN-6131, SN-6132, SN-18071, bisquaternary ammonium heterocycles; Supercoiling
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(93)81678-S

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.