R. Dalbies et al., LINKAGE ISOMERIZATION REACTION OF INTRASTRAND CROSS-LINKS IN TRANS-DIAMMINEDICHLOROPLATINUM(II)-MODIFIED SINGLE-STRANDED OLIGONUCLEOTIDES, Nucleic acids research, 23(6), 1995, pp. 949-953
The stability of trans-{Pt(NH3)(2)[d(CGAG)-N7-G, N7-G]} adducts, resul
ting from cross-links between two guanine residues at d(CGAG) sites wi
thin single-stranded oligonucleotides by trans-diamminedichloroplatinu
m(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 rearran
ge 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 natu
re and concentration of the salt (NaCl or NaClO4) in the range 10-400
mM. The reaction rate depends upon temperature, the t(1/2) values for
the disappearence of the (G,G) intrastrand crosslink 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 tetram
er 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 observe
d with the C residue adjacent to the adduct on the 3' side. It is prop
osed that the linkage isomerization reaction results from a direct att
ack of the base residue on the platinum(II) square complex.