Comparison of DNA complex formation behaviour for two closely related lexitropsin analogues

Two closely related lexitropsin analogues that differ only in the form of the headgroup functionality (CHO (for 1) vs. Ac (for 2)) have been studied in their DNA-binding capacity for the sequence d(GCATATATGC) using 1H-NMR spectroscopy. DNA-Complex formation for the CHO derivative was apparent from the observation of new NMR signals on titration of DNA with ligand. Detailed investigation and assignment of the data for a ligand/DNA-duplex ratio of 2 : 1 clearly delineated the structure as one associated with the minor groove class of DNA complexes. The structure of the complex was determined on the basis of the acquired NMR data. Features characteristic of typical 2 : 1 minor-groove complexes were apparent. In a similar experimental approach, the Ac analogue ligand-DNA binding response was investigated. Despite the close similarity in chemical structure to the CHO case, the Ac analogue was found to produce NMR data of a much poorer quality. This was attributed to more rapid on/off chemical exchange equilibrium between ligand and DNA. From close analysis and comparison of the NMR data for the Ac and CHO headgroup ligand-DNA complexes, it was possible to ascertain that the same type of complex formed in each case but with different relative binding constants. Consideration of the nature and form of these complexes has been made with reference to a previously determined structure from our laboratory for the related lexitropsin analogue thiazotropsin A.