Effects of bifunctional netropsin-related minor groove-binding ligands on mammalian type I DNA topoisomerase.
We investigated the effects of compounds with two covalently linked netropsin moieties (bis-netropsin) on the function of mammalian type I DNA topoisomerase (topo I) in vitro. We initiated these studies because earlier studies had shown that certain bis-netropsins possess a several-fold higher antitumor and antiviral activity than netropsin. We confirmed that the parent compound netropsin, but not its bifunctional derivatives, induce supercoils in closed DNA. We determined that bis-netropsins inhibit the binding of topo I to DNA more efficiently than netropsin and that bis-netropsins but not netropsin induce specific DNA strand cleavage in the presence of topo I. We discuss a model explaining the different effects of netropsin and bis-netropsins on topo I.
Wang
Z
Z
Division of Biology, University of Konstanz, Germany.
Zimmer
C
C
Lown
J W
JW
Knippers
R
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009429:Netropsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D009429:Netropsin; C032161:bis-netropsin; D004247:DNA