Abstract

By automated synthesis, we prepd. hybrid oligonucleotides consisting of covalently linked RNA and p-DNA sequences (p-DNA = 3'-deoxyribopyranose (4'->2')-oligonucleotides). The pairing properties of corresponding hybrid duplexes formed from fully complementary single strands were investigated. An uninterrupted p-p-stacking at the p-DNA/RNA interface and cooperative pairing between the two systems was achieved by connecting them via a 4'-p-DNA-2'->5'-RNA-3' and 5'-RNA-2'->4'-p-DNA-2' phosphodiester linkage, resp. The RNA 2'-phosphoramidites required for the formation of the RNA-2'->4'-p-DNA phosphodiester linkage were synthesized from the corresponding, 3'-O-tom-protected ribonucleosides (tom = [(triisopropylsilyl)oxy]methyl). Analogs of the FMN binding aptamer and the hammerhead ribozyme were prepd. Each of these analogs consisted of two p-DNA/RNA hybrid single strands with complementary p-DNA sequences, designed to substitute stem/loop and stem motifs within the parent compds. By comparative binding and cleavage studies, it was found that mixing of the two complementary p-DNA/RNA hybrid sequences resulted in the formation of the fully functional analogs of the FMN-binding aptamer and of the hammerhead ribozyme, resp. [on SciFinder (R)]

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