Sequence specificity and reactivity of the binding of phenazine-tethered platinum complexes to DNA

An in vitro transcription assay was used to probe the sequence specificity of the binding of phenazine-tethered platinum complexes to DNA, It was foun d that when compared to cis-dichloro(ethylenediamine)platinum(II), the numb er of RNA polymerase blockage sites was increased by similar to 50% and the blockage sites were broadened by 1-3 nucleotides by the presence of the ph enazine ligand. The rate of platination was also enhanced by the presence o f the intercalator, and the increase in the kinetics of platination resulte d in increased levels of adducts formed (i.e. high drug occupancy) as detec ted under conditions of active transcription. The level of platination by d erivative 3 was 20-fold greater than that of the reference compound, which lacked a tethered intercalating phenazine group.