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Ranking ligand affinity for the DNA minor groove by experiment and simulation

Wittayanarakul, Kitiyaporn and Anthony, N.G. and Treesuwan, Witcha and Hannongbua, Supa and Alniss, Hasan and Khalaf, A.I. and Suckling, C.J. and Parkinson, J.A. and Mackay, Simon P. and , Royal Golden Jubilee Ph.D. Program (Funder) and , Thailand Research Fund (Funder) and , W.T. and EPSRC (Funder) and , Scottish Funding Council (Funder) (2010) Ranking ligand affinity for the DNA minor groove by experiment and simulation. Medicinal Chemistry Letters, 1 (8). pp. 376-680. ISSN 1948-5875

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    Abstract

    The structural and thermodynamic basis for the strength and selectivity of the interactions of minor-groove binders (MGBs) with DNA is not fully understood. In 2003 we reported the first example of a thiazole containing MGB that bound in a phase shifted pattern that spanned 6 base-pairs rather than the usual 4 (for tricyclic distamycin-like compounds). Since then, using DNA footprinting, nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and molecular dynamics, we have established that the flanking bases around the central 4 being read by the ligand have subtle effects on recognition. We have investigated the effect of these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand affinity against varying DNA sequences.

    Item type: Article
    ID code: 27548
    Keywords: ligand affinity, DNA minor groove, minor groove binders, DNA footprinting, NMR spectroscopy, isothermal titration calorimetry, molecular dynamics, experiment, simulation, Chemistry, Biochemistry, Organic Chemistry, Drug Discovery
    Subjects: Science > Chemistry
    Department: Faculty of Science > Pure and Applied Chemistry
    Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Related URLs:
    Depositing user: Ms Carol Khalaf
    Date Deposited: 06 Oct 2010 11:36
    Last modified: 27 Mar 2014 21:11
    URI: http://strathprints.strath.ac.uk/id/eprint/27548

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