Binding of platinum and palladium metallointercalation reagents and antitumor drugs to closed and open DNAs.

作者： Mary Howe-Grant , Kun C. Wu , William R. Bauer , Stephen J. Lippard

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摘要: The interaction of platinum and palladium complexes with closed nicked circular linear DNAs was investigated by a variety methods. Cationic metal containing flat, aromatic ligands, such as 2,2',2''-terpyridine, o-phenanthroline, 2,2'-bipyridine, interfere the usual fluorescence enhancement ethidium bromide competing for intercalation sites on calf-thymus DNA. Metal having kinetically exchangable including antitumor drugs cis-[(NH3)2PtCl2] [(en)PtC12], inhibit noncompetitively DNA-associated binding covalently to bases blocking potential sites. Only metallointercalators were capable altering DNA duplex winding, judged effects these reagents upon electrophoretic mobility sedimentation behavior PM-2 DNAs. Long-term (t greater than 120 h) interactions I, I0, II, corresponding superhelical, relaxed, circles, respectively, showed that covalent occurs most readily possibly because presence underwound regions in this tightly wound superhelical active cis-[(NH3)2PtC12] [(en)PtC12] bind I under conditions where inactive trans- [(NH3)2PtC12] does not. Most studied producing chain scissions PM-2DNA I. Exceptions are inert [(bipy)Pt(en)]2+ (terpy)Pt(SCH2CH2OH)]+, suggesting might be prerequisite nicking.

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Binding of platinum and palladium metallointercalation reagents and antitumor drugs to closed and open DNAs.

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Binding of platinum and palladium metallointercalation reagents and antitumor drugs to closed and open DNAs.

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