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
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.
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