cis-diamminedichloroplatinum(II) induced distortion of a single and double stranded deoxydecanucleosidenonaphosphate studied by nuclear magnetic resonance.
The structural distortion of a single- and a double-stranded decadeoxynucleotide upon binding of cis-PtCl2(NH3)2 was studied by 1H-NMR. After selective platination of d(T-C-T-C-G-G-T-C-T-C) (I) at the central d(-GpG-) site (resulting in I-Pt), several non-exchangeable base protons as well as H1', H2', H2" and H3' protons could be assigned by means of conventional NMR double-resonance techniques. Addition of the complementary decamer strand to I and I-Pt yielded the double-stranded III and III-Pt, respectively. All non-exchangeable base, H1', and most of the H2' and H2" protons in the two double stranded compounds could be assigned using 2D-chemical shift correlation (COSY) and nuclear Overhauser enhancement (NOESY) techniques. The double stranded compound III appears to adopt a B-DNA like structure. Comparison of NOEs and proton-proton coupling constants in the d(-GpG-).cisPt part in I-Pt and III-Pt reveals that their structure displays large similarity. Significant chemical shift changes (i.e. larger than 0.1 ppm) between III and III-Pt are restricted to the central four base pairs. It follows that the outer three base pairs, located on either side of the central four base pairs in III-Pt are likely to adopt a regular B-DNA type helix. The observed large upfield and downfield chemical shifts in the d(-CpGpG-) part of III with respect to III-Pt can be rationalized by describing the distortion of the double helix as a kink. A discussion of the observed physical effects upon platination of a double-stranded oligonucleotide is presented.
D001483:Base Sequence; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004277:DNA, Single-Stranded / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*
D004277:DNA, Single-Stranded; D009838:Oligodeoxyribonucleotides; D002945:Cisplatin