NMR Evidence for Sequence-Specific DNA Minor Groove Binding by Bis(ethylenediamine)platinum(II)

Abstract

1H NMR spectroscopy was used to study the binding of Pt(en)22+ to the dodecanucleotides d(CAATCCGGATTG)2 and d(TCGGGATCCCGA)2. Addition of Pt(en)22+ to d(CAATCCGGATTG)2 induced a significant and selective change in the chemical shift of the A3H2 resonance but only small shifts for the major groove base resonances. Similarly, addition of Pt(en)22+ to d(TCGGGATCCCGA)2 induced a selective change in the chemical shift of the A6H2 resonance. In the NOESY spectrum of d(CAATCCGGATTG)2 with added Pt(en)22+ intermolecular NOE cross-peaks between the methylene protons of the metal complex and the H2 of A3 and A9, as well as the H1‘ of T4, T10, and T11 were observed. Importantly, no NOE cross-peaks from the metal complex to either major groove protons or guanine and cytosine protons were observed. In the NOESY spectrum of d(TCGGGATCCCGA)2 with added Pt(en)22+ intermolecular NOE cross-peaks from the metal complex were only observed to the H2 and H1‘ protons of A6 and the T7H1‘ proton. The results demonstrate that the square planar metal complex Pt(en)22+ selectively binds AT sequences in the DNA minor groove.