Cytotoxic trans-oriented iminoether platinum complexes - Kinetics of binding to DNA oligonucleotides determined by N NMR spectroscopy |
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Authors: | Cecilie Alvheim Jo Vinje Giovanni Natile Rongrong Huang |
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Affiliation: | a Department of Chemistry, University of Bergen, Allègt. 41, 5007 Bergen, Norway b Dipartimento Farmaco-Chimico, University of Bari, via E. Orabona 4, I-70125 Bari, Italy c Department of Chemistry, University of Science and Technology of China, Hefei, China |
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Abstract: | The kinetics of reactions between cytotoxic trans-oriented iminoether platinum complexes and DNA oligonucleotides have been studied by 1D and 2D [1H, 15N] HMQC NMR spectroscopy. The results for the two isomers of the mono-iminoether compound trans-[PtCl2(NH3){E/Z-HNC(OMe)Me}] (trans-E and trans-Z) are compared with those of the bis-iminoether derivative trans-[PtCl2{E-HNC(OMe)Me}2] (trans-EE). Earlier we have shown that quite unexpectedly, trans-EE is practically inert towards a central GG residue in a 12-mer double-helical duplex. We now show that the less bulky trans-E and trans-Z compounds do bind to the interior of the duplex [5′-d(G1G2T3A4C5C6G7G8 T9A10C11C12)]2 which contains terminal and central “hot” GG site. The platination by trans-E and trans-Z is as expected most pronounced for the solvent exposed, terminal GG-step but significantly, competitive binding is also observed for the central GG-step. The rate of platination of the terminal G-sites is almost an order of magnitude larger for the oligomer than for the monomer GMP which was studied for comparison. The role of trans-platinum carrier ligands in influencing the type and rate of formation of adducts with DNA and other relevant biomolecules is discussed. |
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Keywords: | Antitumor agents Trans-platinum Iminoether DNA Kinetics NMR |
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