Rearrangement of a 1,3-trans-[Pt(NH3)2[(GXG)-N7G,N7G]] intrastrand cross-link into interstrand cross-links within RNA duplexes.

The cross-linking reaction described previously in the DNA and 2'-O-methyl RNA series is extended to RNA duplexes. A 17mer single-stranded RNA containing the 1,3-trans-[Pt(NH3)2[(GAG)-N7G,N7G]] intrastrand chelate, named GAG (* indicating a platinated base) gives, upon pairing with the complementary RNA strand, the GAG/CUC interstrand cross-link. The rate of the reaction in 200 mM NaClO4 is similar to that observed for DNA-RNA duplexes. It depends on the added Na+ or Mg2+ cation and on its concentration. RNA duplexes containing GA/GA or AG/AG tandem mismatches in the rearrangement triplet core were also studied. The major interstrand cross-links, GAG/CGA and GAG/AGC, are accompanied by a minor one involving the central G of the CGA or AGC complementary sequence GAG/CGA and GAG/AGC. In 200 mM NaClO4, the GA/GA tandem mismatch does not modify the rate of the cross-linking rearrangement whereas the AG/AG mismatch slows it down by a factor of four. Our results reflect the predominance of the local structure of the rearrangement core over the nucleophility of the cross-linking base. They also show that the reaction could be used to trap tertiary structures of naturally occurring RNAs, including those with the commonly encountered GA/GA mismatch.