INTERSTRAND CROSS-LINKING REACTION IN TRANSPLATIN-MODIFIED OLIGO-2'-O-METHYL RIBONUCLEOTIDE-RNA HYBRIDS

In the context of developing an approach to irreversibly and specifica lly link oligonucleotides to RNA, the purpose of this work was to dete rmine the factors interfering with the rate of the rearrangement of th e transplatin 1,3-intrastrand crosslinks into interstrand crosslinks, rearrangement triggered by the formation of a double helix between pla tinated oligo-2'-O-methyl-ribonucleotides and their complementary stra nds, The rate of the rearrangement has been studied as a function of t he length of the hybrids, the location of the intrastrand crosslinks, the nature of the oligonucleotide backbone, and the nature of the doub let replacing the triplet complementary to the intrastrand crosslinks, The thermal stability of the platinated hybrids has been determined i n various salt conditions, The results are discussed in relation to th e mechanism of the rearrangement, It is shown that the cellular protei ns present weaker nonspecific interactions with single-stranded platin ated oligo-2'-O-methyl-nucleotides than with the isosequential oligode oxyribonucleotides.