THE SOLUTION STRUCTURE OF A DNA DUPLEX CONTAINING THE CIS-PT(NH3)(2)[D(-GTG-)-N7(G), N7(G)] ADDUCT, AS DETERMINED WITH HIGH-FIELD NMR AND MOLECULAR MECHANICS/DYNAMICS

The solution structure of the cis-Pt-GTG adduct in the double-stranded oligomer d(CTCTAGTG-CTCAC).td(GTGAGCACTAGAG) was studied with high-resolution NMR techniques. For model building, the distance information obtained from two-dimensional NOE experiments was used in molecular mechanic computations and molecular dynamic structure refinements. The structural distortion upon platination appears to be restricted to the base pairs Pt-G6.C21 and T7.A20; Pt-G8.C19 forms a normal Watson-Crick base pair. T7 is positioned in the minor groove and stacks with the highly propeller-twisted Pt-G6. There is no hydrogen bonding between T7 and A20. The complementary strand is undistorted; A20 stacks with its flanking cytidines (C19 and C21) as in regular B-DNA. The duplex is locally unwound (from base pair A5.T22 to G8.C19: 19 degrees) and is slightly kinked (20 degrees) at the platination site. The platinum coordination distorts the DNA structure at the 5' side of the platinated -GTG- sequence and changes the minor groove face.