DNA CONFORMATIONAL CHANGE PRODUCED BY THE SITE-SPECIFIC INTERSTRAND CROSS-LINK OF TRANS-DIAMMINEDICHLOROPLATINUM(II)

The DNA distortion produced by the interstrand cross-link of trans-dia mminedichloroplatinum-(II) has been described by means of gel electrop horesis, chemical probes, and molecular mechanics modeling. Synthetic double-stranded oligodeoxyribonucleotides of varying lengths (19-22 ba se pairs) were synthesized that contained a unique site-specific inter strand cross-link within their central sequence d(TGCT)/d(AGCT) betwee n complementary guanine and cytosine residues. We find that the platin ated deoxyriboguanosine residue adopts syn conformation. The duplex is distorted on both sides of the cross-link, but the bases are still pa ired. The distortion introduces some flexibility into the helix. In ad dition, the double helix is unwound and bent toward the major groove.