Analytical Chemistry and Spectroscopy
Wiley InterScience Backfile Collection 1832-2000
Chemistry and Pharmacology
The interaction of an analogue of distamycin, FCE-24517, with the ‘AT-rich’ DNA fragment d(CGTATACG)2, was studied in solution by the combined usage of 2D techniques, TOCSY, NOESY, ROESY and 13C/1H shift correlation experiments. The formation of the complex destroys the C2 symmetry of the double helix, leading to a doubling of the nucleotide resonances. Proton and carbon atoms were assigned in the complex in terms of specific strand and residue. The imino protons of the base pairs, involved in hydrogen bonding and the H-2 protons of adenine moieties, were determinant for defining the binding sites of the drug. The presence of multiple equilibrium reactions was proved by means of NOESY and ROESY spectra, where all the chemical-exchange cross peaks were analysed. The FCE-24517 signals in the complex were attributed and some stereospecific assignments performed. Two sets of resonances for FCE were identified, showing that the drug exists in two different chemical environments, corresponding to two different modes of binding in slow chemical exchange. Significant intermolecular NOE interactions between the drug and the nucleotide have allowed the binding sites in the minor groove of the DNA fragment to be located.
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