NMR evidence for sequence-specific DNA minor groove binding by bis(ethylenediamine)platinum(II)

H-1 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 H-2 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.