Linkage isomerization reaction of intrastrand cross-links in trans-diamminedichloroplatinum(II)-modified single-stranded oligonucleotides.
The stability of trans-(Pt(NH3)2[d(CGAG)-N7-G,N7-G]) adducts, resulting from cross-links between two guanine residues at d(CGAG) sites within single-stranded oligonucleotides by trans-diamminedichloro-platinum(II), has been studied under various conditions of temperature, salt and pH. The trans-(Pt(NH3)2[d(C GAG)-N7-G,N7-G]) cross-links rearrange into trans-(Pt(NH3)2[d(CGAG)-N3-C,N7-G]) cross-links. The rate of rearrangement is independent of pH, in the range 5-9, and of the nature and concentration of the salt (NaCl or NaCIO4) in the range 10-400 mM. The reaction rate depends upon temperature, the t1/2 values for the disappearance of the (G,G) intrastrand cross-link ranging from 120 h at 30 degrees C to 70 min at 80 degrees C. The linkage isomerization reaction occurs in oligonucleotides as short as the platinated tetramer d(CGAG). Replacement of the intervening residue A by T has no major effect on the reaction. The C residue adjacent to the adduct on the 5' side plays a key-role in the reaction; its replacement by a G, A or T residue prevents the reaction occuring. No rearrangement was observed with the C residue adjacent to the adduct on the 3' side. It is proposed that the linkage isomerization reaction results from a direct attack of the base residue on the platinum(II) square complex.
Dalbiès
R
R
Centre de Biophysique Moléculaire, CNRS, Orleans, France.
Boudvillain
M
M
Leng
M
M
D001483:Base Sequence; D002945:Cisplatin / Q000737:chemistry*; D003432:Cross-Linking Reagents; D018736:DNA Adducts / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D010472:Perchlorates; D012965:Sodium Chloride; D017670:Sodium Compounds; D013237:Stereoisomerism; D013696:Temperature
D003432:Cross-Linking Reagents; D018736:DNA Adducts; D010472:Perchlorates; D017670:Sodium Compounds; C057270:cisplatin-DNA adduct; C034697:transplatin; D012965:Sodium Chloride; C031068:sodium perchlorate; D002945:Cisplatin