Unwinding in an undecamer double-helical DNA fragment, after binding of cis-diamminedichloroplatinum to a d(-GpTpG-) sequence

Abstract

Unwinding in an Undecamer Double-Helical DNA Fragment, after Binding of c/s-PtCl2(NH3)2 to a d(-GpTpG-) Sequence Sir:Binding of the antitumor drug tii-PtCl2(NH3)2 (cw-DDP15) to DNA is supposed to be a main event in its mechanism of action.1 Difunctional binding of m-DDP to two adjacent guanine bases in the same strand of DNA appears to be the most frequently occurring lesion.2 Other intrastrand binding modes of tis-DDP observed are to a d(-ApG-) fragment3 and to two guanines, separated by a third base. The latter mode of binding was proposed-on the basis of the observation that base-pair mutations are caused by c/'j-DDP, in the LacI gene of Escherichia coli-to take place in d(-G-A-G-) and d(-G-C-G-) nucleotide sequences in particular.4 Subsequently, Marcelis et al.5 showed that, after reaction of the trinucleotide diphosphate d(GpCpG) with ds-DDP, cii-Pt(NH3)2(d(GpCpG)-Ar7(/)vV7(J))6 was formed as the main (>90%) reaction product.The distortion of the structure of DNA, after ris-DDP binding, is expected to be different for the various lesions. After investigating the distortion of a decamer double helix due to chelation at a d(-GpG-) fragment,7 we now report an analogous study of a binding at a d(-GpTpG-) site in a undecanucleoside decaphosphate. It was decided not to use -GAGbecause of the possibility of AG chelation,3 whereas -GCGwas avoided because of the possible complications in case of self-association. It appeared that, in contrast to the d(-GpG-) case, two base pairs are dissociated, even at 0 °C. Moreover, the lowering of the melting temperature as a result of platination appears to be more severe in the d(-GpTpG-) case.

Carboplatin interaction with calf-thymus DNA: A FTIR spectroscopic approach

“…Two adjacent guanines d(GpG) and, adjacent adenine and guanine d(ApG) residues are involved in intrastrand cross-links. This crosslinking results in unwinding and bending of the DNA duplex [6][7][8]. These changes in DNA structures hamper DNA replication and transcription.…”

Cisplatin GG-crosslinks within single-stranded DNA: Origin of the preference for left-handed helicity

“…For instance, in TG*G*, the T nucleotide has a syn conformation [8], whereas in CG*G*, C is anti [34]. Nevertheless, the similarity of the chemical shifts of the G*G* fragment in TG*G* versus CG*G* (Tab.…”

Cis-diamminedichloroplatinum(II) Induced Distortion of a Single and Double Stranded Deoxydecanucleosidenona-phosphate Studied by Nuclear Magnetic Resonance

“…From a comparison of the imino proton chemical shifts, again the conclusion can be drawn that the distortion of the helix is limited to the central four bare pairs, therefore, a more thorough comparison of this part of III and III-Pt seems appropriate. 10. h (ppm) 9. analogous signal in an undecamer double helical fragment (16). Table IV lists the chemical shift differences between III and III-Pt (an upfield shift due to platination is denoted as positive).…”

“…Therefore, investigations were recently started on the distortion induced by reaction of cis-DDP to a d(-GpG-), d(-GpNpG-) or d(-ApG-) sequence in one of the strands (14,15,16) of well-defined double stranded oligonucleotides.…”