A 1H and 31P NMR study of cis‐Pt(NH3)2 [d(CpGpG)‐N7 (2),N7 (3)] The influence of a 5′‐terminal cytosine, on the structure of the cis‐Pt(NH3)2 [d(GpG)‐N7,N7] instrastrand cross‐link

Abstract

Proton NMR studies at 300 MHz and 500 MHz have been carried out on the trinucleoside bisphosphate d(CpGpG) and on cis‐Pt(NH₃)₂[d(CpGpG)‐N7 (2),N7 (3)] [abbreviated as d(CpGpGp) ·cisPt]. For the Pt adduct, ¹³C and ³¹P NMR was also used for characterizing the oligonucleotide. d(CpGpG) appears to revert to a B‐DNA‐type single helix at lower temperatures. The relatively small concentration dependence of the proton chemical shifts, in comparison with shifts due to intramolecular stacking effects, indicates that the compound is essentially single‐stranded. In d(CpGpGp) ·cisPt, the first nucleoside, C(1), stacks well on top of the second, G(2), despite the N conformation of the G(2) sugar ring. The platinated GpG part in this trimer adopts largely the same structure as in cis‐Pt(NH₃)₂[d(GpGpG)‐N7 (1),N7 (2)] [den Hartog, J. H. J., et al. (1982) Nucleic Acids Res. 10, 4715–4730]. Main differences however, are changes in H8 chemical shifts and a 0.6‐ppm downfield shift of the third nucleotide phosphorus, P(3), in d(CpGpGp) ·cisPt with respect to P(2) in d(GpG) ·cisPt. The latter shift change is likely to be induced by a structural alteration, caused by stacking of C(1) on top of G(2). Also, the large chemical shift differences between the two H8 protons in d(NpGpG) ·cisPt fragments is discussed; the deviation from a mirror symmetry of the two guanine bases seems to be the main origin of this effect. The chemical shift changes, observed in the proton and phosphorus NMR chemical shift temperature and chemical shift pH profiles have been explained in terms of stack‐destack equilibria changes.