Why Pentose‐ and Not Hexose‐Nucleic Acids??. Part VII. Pyranosyl‐RNA (‘p‐RNA’). Preliminary communication

Abstract

Qualitative conformational analysis of the entirety of conceivable hexo‐ and pentopyranosyl oligonucleotide systems derived from the diastereoisomeric aldohexoses (CH2O)6 and aldopentoses (CH2O)5 predicts the existence of a variety of pairing systems which have not been experimentally investigated so far. In particular, the analysis foresees the existence of a ribopyranosyl isomer of RNA (‘p‐RNA’), containing the phosphodiester linkage between the positions C(4′) and C(2′) of neighboring ribopyranosyl units. Double strands of p‐RNA oligonucleotides are expected to have a linear structure and to show purine‐pyrimidine and purine‐purine (Watson‐Crick) pairing comparable in strength to that observed in homo‐DNA. Experimentally, synthetic β‐D‐ribopyranosyl (4′→2′)‐oligonucleotides derived from adenine and uracil confirm this prognosis: adenine‐uracil pairing in p‐RNA duplexes is stronger than in the corresponding RNA duplexes. Importantly, adenine in p‐Ribo(A8) does not show (reverse‐Hoogsteen) self‐pairing, in sharp contrast to its behavior in the homo‐DNA series. The sheer existence of strong and selective pairing in a system that is constitutionally isomeric to RNA and can be predicted to have a linear structure has implications for the problem of RNA's origin. In this context, a comprehensive experimental study of the pairing properties of p‐RNA, of its potential for constitutional assembly, self‐replication, and intra‐duplex isomerization to RNA seems mandatory.