First look at RNA in l-configuration

• Published in: Acta crystallographica. Section D, Biological crystallography. Vol. 60; no. 1; pp. 1 - 7
• Main Authors: Vallazza, M., Perbandt, M., Klussmann, S., Rypniewski, W., Einspahr, H. M., Erdmann, V. A., Betzel, Ch
• Format: Journal Article
• Language: English
• Published: 5 Abbey Square, Chester, Cheshire CH1 2HU, England Munksgaard International Publishers 01-01-2004
• Subjects: Base Pairing; Crystallization; Crystallography, X-Ray; l-oligonucleotides; l-RNA; Models, Molecular; Nucleic Acid Conformation; RNA - chemistry; RNA, Bacterial - chemistry; RNA, Ribosomal, 5S - chemistry; Spiegelmers; Stereoisomerism
• DOI: 10.1107/S0907444903027690
• EISSN: 1399-0047
• ISSN: 1399-0047; 0907-4449

Nucleic acid molecules in the mirror image or l‐configuration are unknown in nature and are extraordinarily resistant to biological degradation. The identification of functional l‐­oligonucleotides called Spiegelmers offers a novel approach for drug discovery based on RNA. The sequence r(CUGGGCGG)·r(CCGCCUGG) was chosen as a model system for structural analysis of helices in the l‐configuration as the structure of the d‐form of this sequence has previously been determined in structural studies of 5S RNA domains, in particular domain E of the Thermus flavus 5S rRNA [Perbandt et al. (2001), Acta Cryst. D57, 219–224]. Unexpectedly, the results of crystallization trials showed little similarity between the d‐ and the l‐forms of the duplex in either the crystallization hits or the diffraction performance. The crystal structure of this l‐RNA duplex has been determined at 1.9 Å resolution with Rwork and Rfree of 23.8 and 28.6%, respectively. The crystals belong to space group R32, with unit‐cell parameters a = 45.7, c = 264.6 Å. Although there are two molecules in the asymmetric unit rather than one, the structure of the l‐form arranges helical pairs in a head‐to‐tail fashion to form pseudo‐continuous infinite helices in the crystal as in the d‐form. On the other hand, the wobble‐like G·C+ base pair seen in the D‐RNA analogue does not appear in the l‐RNA duplex, which forms a regular double‐helical structure with typical Watson–Crick base pairing.