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

1 H NMR spectroscopy was used to study the binding of Pt(en) 2 2+ to the dodecanucleotides d(CAATCCGGATTG) 2 and d(TCGGGATCCCGA) 2 . Addition of Pt(en) 2 2+ to d(CAATCCGGATTG) 2 induced a significant and selective change in the chemical shift of the A 3 H2 resonance but only small shifts for the major groove base resonances. Similarly, addition of Pt(en) 2 2+ to d(TCGGGATCCCGA) 2 induced a selective change in the chemical shift of the A 6 H2 resonance. In the NOESY spectrum of d(CAATCCGGATTG) 2 with added Pt(en) 2 2+ intermolecular NOE cross-peaks between the methylene protons of the metal complex and the H2 of A 3 and A 9, as well as the H1‘ of T 4, T 10, and T 11 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) 2 2+ intermolecular NOE cross-peaks from the metal complex were only observed to the H2 and H1‘ protons of A 6 and the T 7 H1‘ proton. The results demonstrate that the square planar metal complex Pt(en) 2 2+ selectively binds AT sequences in the DNA minor groove.