Pyranosyl‐RNA (‘p‐RNA’): Base‐pairing selectivity and potential to replicate. Preliminary communication

Abstract

Base pairing in p‐RNA (β‐D‐ribopyranosyl‐(4′ → 2′)‐oligonucleotides) is not only stronger than in DNA and RNA, but also more selective in the sense that it is strictly confined to the Watson‐Crick mode. Homopurine sequences (tested up to decamers) exist as single strands under conditions where they undergo reverse‐Hoogsteen self‐pairing in homo‐DNA or Hoogsteen self‐pairing in DNA. This exceptional pairing selectivity is rationalized as hinging on two structural features of p‐RNA: the large inclination between backbone axis and base‐pair axes in p‐RNA duplexes, and the higher rigidity of the p‐RNA backbone compared with RNA, DNA, and homo‐DNA. The most important consequence of the pairing selectivity refers to the potential of p‐RNA to replicate. Replicative copying of sequence information by nonenzymatic template‐controlled ligation is not hampered by self‐pairing of guanine‐rich templates, as it is known to be the case in the RNA series. We have demonstrated two replicative cycles in which G‐rich p‐RNA‐octamer templates induce sequence‐selective ligation of tetramer‐2′‐phosphate derivatives to complementary C‐rich octamer sequences, and in which the latter, with comparable efficiency, induce corresponding ligation reactions back to the original G‐rich octamers. Ligation is most satisfactorily achieved after pre‐activation of the 2′‐phosphate groups as 2′,3′‐cyclophosphate derivatives; in this version, the process does not proceed as oligocondensation, but as a genuine oligo…