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

Kitiyaporn Wittayanarakul, Nahoum G. Anthony, Witcha Treesuwan, Supa Hannongbua, Hasan Alniss, Abedawn I. Khalaf, Colin J. Suckling, John A Parkinson, Simon P. Mackay

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11 Citations (Scopus)
137 Downloads (Pure)


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.
Original languageEnglish
Pages (from-to)376-680
Number of pages5
JournalMedicinal Chemistry Letters
Issue number8
Early online date30 Jul 2010
Publication statusPublished - 11 Nov 2010


  • ligand affinity
  • DNA minor groove
  • minor groove binders
  • DNA footprinting
  • NMR spectroscopy
  • isothermal titration calorimetry
  • molecular dynamics
  • experiment
  • simulation


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