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  • Competitive formation of both long-range 5'-5' and short-range antiparallel 3'- 3' DNA interstrand cross-links by a trinuclear platinum complex on binding to a 10-mer duplex

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    Author(s)
    Ruhayel, Rasha A
    Berners-Price, Susan J
    Farrell, Nicholas P
    Griffith University Author(s)
    Berners-Price, Sue J.
    Ruhayel, Rasha
    Farrell, Nicholas
    Year published
    2013
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    Abstract
    2D [1H, 15N] HSQC NMR spectroscopy has been used to monitor the reaction of fully 15N-labelled [{trans-PtCl(NH3)2}2(μ-trans-Pt(NH3)2{NH2(CH2)6NH2}2)]4+ (Triplatin, BBR3464 or 1,0,1/t,t,t (15N-1)) with the self-complementary 10-mer DNA duplex 5′-{d(ACGTATACGT)2} (duplex I) at pH 5.4 and 298 K. Initial electrostatic interactions were observed in the minor groove of the duplex, followed directly by aquation to form the monoaqua monochloro species. There was evidence for two discrete monofunctional adducts, through covalent binding at the guanine N7 sites, and one had distinctly different 1H/15N chemical shifts to those observed ...
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    2D [1H, 15N] HSQC NMR spectroscopy has been used to monitor the reaction of fully 15N-labelled [{trans-PtCl(NH3)2}2(μ-trans-Pt(NH3)2{NH2(CH2)6NH2}2)]4+ (Triplatin, BBR3464 or 1,0,1/t,t,t (15N-1)) with the self-complementary 10-mer DNA duplex 5′-{d(ACGTATACGT)2} (duplex I) at pH 5.4 and 298 K. Initial electrostatic interactions were observed in the minor groove of the duplex, followed directly by aquation to form the monoaqua monochloro species. There was evidence for two discrete monofunctional adducts, through covalent binding at the guanine N7 sites, and one had distinctly different 1H/15N chemical shifts to those observed previously in analogous reactions. Bifunctional adduct formation followed by binding at a second guanine N7 site with evidence for both the 3′–3′ 1,2-GG and 5′–5′ 1,6-GG interstrand cross-links in a ratio of 2 : 1. The results show that cross-link preference is kinetically controlled and will depend critically on the reaction conditions, explaining why in a previous reaction of 1 with duplex I the major adduct isolated by HPLC had two simultaneous 3′–3′ 1,2-interstrand cross-links.
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    Journal Title
    Dalton Transactions
    Volume
    42
    Issue
    9
    DOI
    https://doi.org/10.1039/C2DT32079G
    Copyright Statement
    © 2013 Royal Society of Chemistry. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
    Subject
    Bioinorganic Chemistry
    Inorganic Chemistry
    Theoretical and Computational Chemistry
    Other Chemical Sciences
    Publication URI
    http://hdl.handle.net/10072/56145
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    • Journal articles

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