RECOGNITION OF NUCLEIC-ACID DOUBLE HELICES BY HOMOPYRIMIDINE 2',5'-LINKED RNA

We have studied the effect of a 2',5'-RNA third strand backbone on the stability of triple helices with a 'pyrimidine motif' targeting the p olypurine strand of duplex DNA, duplex RNA and DNA/RNA hybrids, Compar ative experiments were run in parallel with DNA and the regioisomeric RNA as third strands adopting the experimental design of Roberts and C rothers,The results reveal that 2',5'-RNA is indeed able to recognize double helical DNA (DD) and DNA (purine):RNA (pyrimidine) hybrids (DR) , However, when the duplex purine strand is RNA and the duplex pyrimid ine strand is DNA or RNA (i.e. RD or RR), tripler formation is not obs erved, These results exactly parallel what is observed for DNA third s trands, Based on T-m data, the affinities of 2',5'-RNA and DNA third s trands towards DD and DR duplexes were similar, The RNA third strand f ormed triplexes with all four hairpins, as previously demonstrated, In analogy to the arabinose and 2'-deoxyribose third strands, the possib le C2'-endo pucker of 2',5'-linked riboses together with the lack of a n alpha-2'-OH group are believed to be responsible for the selective b inding of 2',5'-RNA to DD and DR duplexes, over RR and RD duplexes, Th ese studies indicate that the use of other oligonucleotide analogues w ill prove extremely useful in dissecting the contributions of backbone and/or sugar puckering to the recognition of nucleic acid duplexes.