SINGLE-STRANDED-DNA AND RNA TARGETED TRIPLEX-FORMATION - UV, CD AND MOLECULAR MODELING STUDIES OF FOLDBACK TRIPLEXES CONTAINING DIFFERENT RNA, 2'-OME-RNA AND DNA STRAND COMBINATIONS

We studied the influence of different 2'-OMe-RNA and DMA strand combin ations on single strand targeted foldback tripler formation in the Py. Pu:Py motif using ultraviolet (UV) and circular dichroism (CD) spectro scopy, and molecular modeling. The study of eight combinations of trip lexes (D.D:D, R.D:D, D.D:R*, R*.D:R*, D.R:D, R*.R:D, D.R:R*, and R*.R :R; where the first, middle, and last letters stand for the Hoogsteen Pyrimidine, Watson-Crick [WC] purine and WC pyrimidine strands, respe ctively, and D, R and R stand for DNA, RNA and 2'-OMe-RNA strands, re spectively) indicate more stable foldback tripler formation with a DNA purine strand than with an RNA purine strand. Of the four possible WC duplexes with RNA/DNA combinations, the duplex with a DNA purine stra nd and a 2'-OMe-RNA pyrimidine strand forms the most thermally stable tripler, although its thermal stability is the lowest of all four dupl exes. Irrespective of the duplex combination, a 2'-OMe-RNA Hoogsteen p yrimidine strand forms a stable foldback tripler over a DNA Hoogsteen pyrimidine strand confirming the earlier reports with conventional and circular triplexes. The CD studies suggest a B-type conformation for an all DNA homo-foldback tripler (D.D:D), while hetero-foldback triple r spectra suggest intermediate conformation to both A-type and B-type structures. A novel molecular modeling study has been carried out to u nderstand the stereochemical feasibility of all the combinations of fo ldback triplexes using a geometric approach. The new approach allows u se of different combinations of chain geometries depending on the natu re of the chain (RNA vs. DNA).