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  • Substitution-Inert Polynuclear Platinum Complexes with Dangling Amines: Condensation/Aggregation of Nucleic Acids and Inhibition of DNA-Related Enzymatic Activities

    Author(s)
    Malina, Jaroslav
    Cechova, Klara
    Farrell, Nicholas P
    Brabec, Viktor
    Griffith University Author(s)
    Farrell, Nicholas
    Year published
    2019
    Metadata
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    Abstract
    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 ...
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    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.
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    Journal Title
    INORGANIC CHEMISTRY
    Volume
    58
    Issue
    10
    DOI
    https://doi.org/10.1021/acs.inorgchem.9b00254
    Subject
    Inorganic Chemistry
    Physical Chemistry (incl. Structural)
    Other Chemical Sciences
    Publication URI
    http://hdl.handle.net/10072/385086
    Collection
    • Journal articles

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