Qualitative conformational analysis of the entirety of conceivable hex
o- and pentopyranosyl oligonucleotide systems derived from the diaster
eoisomeric aldohexoses (CH2O)6 and aldopentoses (CH2O)5 predicts the e
xistence of a variety of pairing systems which have not been experimen
tally investigated so far. In particular, the analysis foresees the ex
istence of a ribopyranosyl isomer of RNA ('p-RNA'), containing the pho
sphodiester linkage between the positions C(4') and C(2') of neighbori
ng ribopyranosyl units. Double strands of p-RNA oligonucleotides are e
xpected to have a linear structure and to show purine-pyrimidine and p
urine-purine (Watson-Crick) pairing comparable in strength to that obs
erved in homo-DNA. Experimentally, synthetic beta-D-ribopyranosyl (4'-
2')-oligonucleotides derived from adenine and uracil confirm this prog
nosis: adenine-uracil pairing in p-RNA duplexes is stronger than in th
e corresponding RNA duplexes. Importantly, adenine in p-Ribo(A8) does
not show (reverse-Hoogsteen) self-pairing, in sharp contrast to its be
havior in the homo-DNA series. The sheer existence of strong and selec
tive pairing in a system that is constitutionally isomeric to RNA and
can be predicted to have a linear structure has implications for the p
roblem of RNA's origin. In this context, a comprehensive experimental
study of the pairing properties of p-RNA, of its potential for constit
utional assembly, self-replication, and intra-duplex isomerization to
RNA seems mandatory.