Reactions of platinum(II) complexes with a DNA hairpin, d(CGCGTTGTTCGCG): structural characterization and kinetic studies

Reactions of the platinum complexes cis-[Pt(NH3)2Cl(OH2)]+ (1) and cis-[Pt(NH3)(NH2C6H11)Cl(OH2)]+ (2) with a DNA hairpin, d(CGCGTTGTTCGCG) (DNA I), were investigated as a function of pH and ionic strength. The rates of platination were monitored by HPLC. The sites of reactivity for complexes 1 and 2 were determined by chemical probing with dimethylsulfate (DMS), hydrazine, and Fe(EDTA)2−. The effects of platination on DNA structure and stability were determined by using gel electrophoresis, circular dichroism (CD), and thermal melting. In general, the platinum complexes were most reactive at G7 in the hairpin loop, they caused a destabilization of the DNA hairpin, and they caused a B- to Z-form transition in the DNA conformation.