In memoriam Rolf Scheffold (1. IX.95) Base pairing in p-RNA @ -o-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 Hoogsfeen 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 oligomerization. This is of considerable promise for the search for potentially natural conditions under which homochiral p-RNA strands might self-assemble and self-replicate.

(1 7. X. 96) The solution structure of the duplex formed by self-pairing of the p-RNA octamer B-o-ribopyranosyl-(2' + 4)-(CGAATTCG) was studied by NMR techniques and, independently, by molecular-dynamics calculations. The resonances of all non-exchanging protons, H-bearing C-atoms, P-atoms, and of most NH protons were assigned. Dihedral angle and distance constraints derived from coupling constants and NOESY spectra are consistent with a single dominant conformer and corroborate the main structural features predicted by qualitative conformational analysis. The duplex displays Watson-Crick pairing with antiparallel strand orientation. The dihedral angles p and F in the phosphodiester linkages differ considerably from the idealized values. Model considerations indicate that these deviations from the idealized model allow better inter strand stacking and lessen unfavorable interactions in the backbone. The average base-pair axis forms an angle of cu. 40" with the backbone. The resulting inferstrand n-1~ stacking between either two purines, or a purine and a pyrimidine, but not between two pyrimidines, constitutes a characteristic structural feature of the p-RNA duplex. A 1000-ps molecular-dynamics (MD) calculation with the AMBER force field resulted in an average structure of the same conformation type as derived by NMR. For the backbone torsion angle E, dynamically averaged coupling constants from the MD calculation agree well with the experimental values, but for the anglep, a systematic difference of ca. 25" remains. The two base pairs at the ends of the duplex are calculated to be highly labile, which is consistent with the high exchange rate of the corresponding imino protons found by NMR.

The design of polymers that could mimic biomolecules in their ability to form assemblies similar to ribo- and deoxyribonucleic acids has become an attractive field of chemical research, and NMR spectroscopy has played a vital role in the determination of the three-dimensional structure of these newly designed nonnatural polymers. The structure of a self-complementary octamer duplex of pyranosyl-RNA (pRNA) has been determined by using NMR spectroscopy experimental data and an Xplor structure calculation protocol. The structure has been compared with the structure of a duplex formed by a designed nucleo-delta-peptide analogue of pRNA. The two duplexes assume one predominant conformation and show a high structural similarity. The conformation type of both structures agrees with those predicted based on qualitative conformational analysis and both structures show a good convergence toward the average torsion angles derived by NMR spectroscopy.

The cover picture shows the NMR spectroscopy solution structures of duplex RNA, pyranosyl-RNA, and the ªnucleo-d-peptideº analogue NDP. Storage and transfer of genetic information in biological systems depends on the reversible duplex formation stabilized by complementary Watson±Crick base pairing and the ability to assemble monomers in specific sequences with high fidelity. The design of alternative self-pairing polymers helps in the understanding of the determinants of nucleic acid structure itself. Further details about the comparison of the structures shown can be found in the article by Schwalbe and co-workers on p. 93 ff.

The cover picture shows the NMR spectroscopy solution structures of duplex RNA, pyranosyl-RNA, and the ªnucleo-d-peptideº analogue NDP. Storage and transfer of genetic information in biological systems depends on the reversible duplex formation stabilized by complementary Watson±Crick base pairing and the ability to assemble monomers in specific sequences with high fidelity. The design of alternative self-pairing polymers helps in the understanding of the determinants of nucleic acid structure itself. Further details about the comparison of the structures shown can be found in the article by Schwalbe and co-workers on p. 93 ff.