Sequence-dependent conformational changes in DNA induced by polynuclear platinum complexes.

In this work, the B-->Z transition of poly(dG-dC).poly(dG-dC) and the B-->A transition of poly(dG).poly(dC) and of calf thymus (CT) DNA fragments modified by antitumor bifunctional polynuclear platinum complexes were investigated by circular dichroism (CD). The transition from the B- to Z-form of DNA was inducible with all three compounds studied, as indicated by an inversion of the B-form spectra. The B-->A transition in poly(dG).poly(dC) was induced easily by platinum complex binding alone, while the B-->A transition in CT DNA was induced by ethanol but inhibited by coordination of all polynuclear platinum compounds used here. It was shown that the compound [¿cis-PtCl(NH3)2¿2 mu-¿H2N(CH2)6NH2¿] (NO3)2 (1,1/c,c) was most effective at inhibiting the B-->A transition in CT DNA, and [¿trans-PtCl(NH3)2¿2 mu-¿trans-Pt(NH3)2(H2N(CH2)6NH2)2¿] (NO3)4 (1,0,1/t,t,t) was least effective, while the effectiveness of [¿trans-PtCl(NH3)2¿2 mu-¿H2N(CH2)6NH2¿] (NO3)2 (1,1/t,t) fell between the two. This corresponded to the relative amounts of interstrand crosslinks in double-stranded DNA caused by each compound.