Binding of platinum and palladium metallointercalation reagents and antitumor drugs to closed and open DNAs
| Autor: | Stephen J. Lippard, William R. Bauer, Kun C. Wu, Mary Howe-Grant |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Stereochemistry
Intercalation (chemistry) chemistry.chemical_element Antineoplastic Agents Ligands Biochemistry Metal Structure-Activity Relationship chemistry.chemical_compound Ethidium Binding site Platinum Binding Sites Chemistry DNA Kinetics Spectrometry Fluorescence Covalent bond visual_art visual_art.visual_art_medium Cisplatin DNA Circular Ethidium bromide Mathematics Palladium |
| Zdroj: | Biochemistry. 15:4339-4346 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi00664a031 |
| Popis: | The interaction of platinum and palladium complexes with closed and nicked circular and linear DNAs was investigated by a variety of methods. Cationic metal complexes containing flat, aromatic ligands, such as 2,2',2''-terpyridine, o-phenanthroline, and 2,2'-bipyridine, interfere with the usual fluorescence enhancement of ethidium bromide by competing for intercalation sites on calf-thymus DNA. Metal complexes having kinetically exchangable ligands, including the antitumor drugs cis-[(NH3)2PtCl2] and [(en)PtC12], inhibit noncompetitively the DNA-associated ethidium fluorescence enhancement by binding covalently to the bases and blocking potential intercalation sites. Only the metallointercalators were capable of altering the DNA duplex winding, as judged by the effects of these reagents upon the electrophoretic mobility and sedimentation behavior of PM-2 DNAs. Long-term (t greater than 120 h) interactions of metal complexes with PM-2 DNAs I, I0, and II, corresponding to superhelical, closed relaxed, and nicked circles, respectively, showed that covalent binding occurs the most readily to DNA I, possibly because of the presence of underwound duplex regions in this tightly wound superhelical DNA. The active antitumor drugs cis-[(NH3)2PtC12] and [(en)PtC12] bind covalently to DNA I under conditions where the inactive trans- [(NH3)2PtC12] does not. Most of the complexes studied were capable of producing chain scissions in PM-2DNA I. Exceptions are the kinetically inert complexes [(bipy)Pt(en)]2+ and (terpy)Pt(SCH2CH2OH)]+, suggesting that covalent binding might be a prerequisite for nicking. |
| Databáze: | OpenAIRE |
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