The Solution Structure of a DNA Duplex Containing the cis ‐Pt(NH3)2[d(‐GTG‐)‐N 7(G), N 7(G)] Adduct, as Determined with High‐Field NMR and Molecular Mechanics/Dynamics

Abstract

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°) and is slightly kinked (20°) 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. Copyright © 1994, Wiley Blackwell. All rights reserved