Molecular interaction of DNA with bisplatinum(II) complexes having bis(vicinal 1,2-diamines) as ligand.
The interaction of novel, tetrafunctional bisplatinum compounds with DNA was investigated. These compounds have bis(vicinal 1,2-diamines) as ligand. The reactions' efficiency, types of cross-links, alterations of the global DNA structure, and sequence selectivity differ significantly from the corresponding features of cisplatin. In particular, they form multiple complexes with dsDNA, which include intrastrand, interstrand and interhelical cross-links and cross-links over sticky ends. The novel compounds are able to untwist but not shorten dsDNA. The reactivity and adduct-forming efficiency of these compounds is, depending on the spacer length, 100-200-fold higher than that of cisplatin. As a consequence, interstrand cross-links are also formed to a higher extent. The chemical stability of the interstrand cross-links against cyanide ions, however, is weaker than that of interstrand cross-links formed by cisplatin, suggesting that each platinum sphere of a bisplatinum compound forms intrastrand cross-links. With dsDNA, they show a preference toward purines, particularly guanines, but they apparently are also coordinated to other nucleobases. Their sequence selectivity toward dsDNA is higher than that of cisplatin. Thus, the novel compounds extend the spectrum of alternative platinum-based compounds with chemical features different from cisplatin.
Büning
H
H
Institut für Biochemie der Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 München, Germany.
Altman
J
J
Beck
W
W
Zorbas
H
H
D000970:Antineoplastic Agents / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D003959:Diamines / Q000737:chemistry*; D006147:Guanine / Q000737:chemistry; D009690:Nucleic Acid Conformation; D009944:Organoplatinum Compounds / Q000737:chemistry*
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D003959:Diamines; D009944:Organoplatinum Compounds; D006147:Guanine