Comparative Stability of Triple Helices Containing Modified DNA or RNA Pyrimidine Strands

Abstract

Control of gene expression by oligodeoxyribonucleotide-directed triplex formation, known as antigene therapy (l), is widely studied since works have demonstrated the sequence-specific recognition of double helical DNA by a third strand (2,3). Triplex formation occurs when an oligopyrimidine strand binds in the major groove with a parallel orientation to the purine strand of polypurine polypyrimidine DNA duplex. Binding specificity is obtained from recognition of thymidine and AT base pair and N3 protonated cytosine and GC base pairs to form respectively the isomorphous T:AT and C+:GC triplets via Hoogsteen hydrogen bonding (2,3). Tfiple helix formation involving cytosine is pH dependent. In order to use oligos for antigene therapy, they must fulfill at least two requirements such as nucleases resistance, since wild type DNA and RNA are rapidly degraded by nucleases present in cells and sera (4), and high binding affinity with the complementary double-stranded DNA in order to block the transcription or the replication of the corresponding gene. To accomplish the former point, several modifications of the phcc;We or of the sugar have been proposed (5).