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3′‐Deoxyribopyranose (4′→2′)‐Oligonucleotide Duplexes (= p ‐DNA Duplexes) as Substitutes of RNA Hairpin Structures
Author(s) -
Ackermann Damian,
Wu Xiaolin,
Pitsch Stefan
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200205)85:5<1463::aid-hlca1463>3.0.co;2-q
Subject(s) - chemistry , oligonucleotide , rna , ribozyme , dna , phosphodiester bond , hammerhead ribozyme , hairpin ribozyme , rnase h , aptamer , stereochemistry , vs ribozyme , base pair , biochemistry , microbiology and biotechnology , gene , biology , reverse transcriptase
By automated synthesis, we prepared hybrid oligonucleotides consisting of covalently linked RNA and p ‐DNA sequences ( p ‐DNA=3′‐deoxyribopyranose (4′→2′)‐oligonucleotides) (see Table 1 ). The pairing properties of corresponding hybrid duplexes, formed from fully complementary single strands were investigated. An uninterrupted π ‐ π ‐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, respectively (see Fig. 4 ). The RNA 2′‐phosphoramidites 9 – 12 , 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; Scheme 1 ). Analogues of the flavin mononucleotide (=FMN) binding aptamer 22 and the hammerhead ribozyme 25 were prepared. Each of these analogues 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 compounds. 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 analogues 23 ⋅ 24 and 27 ⋅ 28 of the FMN‐binding aptamer and of the hammerhead ribozyme, respectively.