Pyrimidine motif triplexes containing polypurine RNA or DNA with oligo 2 '-O-methyl or DNA triplex forming oligonucleotides

Tripler forming oligonucleotides (TFOs) are potentially useful in targeting RNA for antisense therapeutic applications. To determine the feasibility o f targeting polypurine RNA with nuclease-resistant oligonucleotides, TFOs c ontaining 2'-deoxy or 2'-O-methyl (2'-OMe) backbones, designed to form pyri midine motif triplexes with RNA, were synthesized. TFOs were made which can form trimolecular triplexes, or bimolecular, 'clamp' triplexes with polypu rine RNA and DNA. It was found that the relative stabilities of the triplex es formed followed the order: M.DM(clamp) >>> D.DD approximate to M.DD > M. RM > D.DM > M.RD approximate to M.DM, where M is a 2'-OMe, D is a DNA and R is an RNA backbone. The third strand is listed first, separated by a dot f rom the purine strand of the Watson-Crick duplex, followed by the pyrimidin e strand of the duplex. The results described here provide insight into the feasibility of using TFOs containing a 2'-OMe backbone as antisense agents . (C) 2000 Elsevier Science B.V. All rights reserved.