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  • Steric Determinants of Pt/DNA Interactions and Anticancer Activity

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    HambleyPUB6923.pdf (1.194Mb)
    Author(s)
    Hambley, TW
    Berners-Price, SJ
    Davies, MS
    Diakos, CI
    Er, HM
    Fenton, RR
    Ling, ECH
    Rezler, EM
    Griffith University Author(s)
    Berners-Price, Sue J.
    Year published
    1998
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    Abstract
    Studies directed at establishing the structural features that control Pt/DNA interactions and the anticancer activity of Pt drugs are described. [H1,N15]-HSQC 2D NMR spectroscopic studies of the reactions of cisplatin with oligonucleotides containing ApG and GpA binding sites reveal dramatic differences in the rates of formation of monofunctional adducts at the two sites. When the reactant is cis-[Pt(NH3)2(OH2)2]2+ no such differences are observed suggesting that outer-sphere interactions between the reactant and the oligonucleotide may play a substantial role in determining the rates. Rates of closure to the bifunctional ...
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    Studies directed at establishing the structural features that control Pt/DNA interactions and the anticancer activity of Pt drugs are described. [H1,N15]-HSQC 2D NMR spectroscopic studies of the reactions of cisplatin with oligonucleotides containing ApG and GpA binding sites reveal dramatic differences in the rates of formation of monofunctional adducts at the two sites. When the reactant is cis-[Pt(NH3)2(OH2)2]2+ no such differences are observed suggesting that outer-sphere interactions between the reactant and the oligonucleotide may play a substantial role in determining the rates. Rates of closure to the bifunctional adducts are similar to those observed for cisplatin. Studies of the adduct profiles formed by sterically bulky and/or optically active complexes reveal that steric interactions play a major role in mediating the binding of Pt(ll) to DNA but that hydrogen bonds play less of a role. In vitro cytotoxic activities for these complexes do not always follow the trends that would be expected on the basis of the adduct profiles.
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    Journal Title
    Metal Based Drugs
    Volume
    5
    DOI
    https://doi.org/10.1155/MBD.1998.197
    Copyright Statement
    © 1998 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Pharmacology and Pharmaceutical Sciences
    Publication URI
    http://hdl.handle.net/10072/181156
    Collection
    • Journal articles

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