The substitution-inert polynuclear platinum complexes (SI-PPCs) are now recognized as a distinct subclass of platinum anticancer drugs with high DNA binding affinity. Here, we investigate the effects of SI-PPCs containing dangling amine groups in place of NH3 as ligands to increase the length of the molecule and therefore overall charge and its distribution. The results obtained with the aid of biophysical techniques, such as total intensity light scattering, gel electrophoresis, and atomic force microscopy, show that addition of dangling amine groups considerably augments the ability of SI-PPCs to condense/aggregate nucleic acids. Moreover, this enhanced capability of SI-PPCs correlates with their heightened efficiency to inhibit DNA-related enzymatic activities, such as those connected with DNA transcription, catalysis of DNA relaxation by DNA topoisomerase I, and DNA synthesis catalyzed by Taq DNA polymerase. Thus, the addition of the dangling amine groups resulting in structures of SI-PPCs, which differ so markedly from the derivatives of cisplatin used in the clinic, appears to contribute to the overall biological activity of these molecules.

Czech Academy of Sciences Institute of Biophysics Kralovopolska 135 CZ 61265 Brno Czech Republic

Department of Chemistry Virginia Commonwealth University Richmond Virginia 23284 2006 United States

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