A two B-Z junction containing DNA resolves into an all right-handed double-helix.

Natural and artificial oligonucleotides are capable of assuming many different conformations and functions. Here we present results of an NMR restrained molecular modelling study on the conformational preferences of the modified decanucleotide d((m)C1G2(m)C3G4C5(L)G6(L)(m)C7G8(m)C9G10) .d((m)C11G12(m)C13G14C15(L)G (L)16(m)C17-G18(m)C19G20 ) which contains L deoxynucleotides in its centre. This chimeric DNA was expected to form a right-left-right-handed B-type double-helix (BB*B) at low salt concentration. Actually, it matured into a fully right-handed double helix with its central C(L)pG(L) core forming a right-handed Z-DNA helix embedded in a B-DNA matrix (BZ*B). The interplay between base-base and base-sugar stackings within the core and its immediately adjacent residues was found to be critical in ensuring the stabilisation of the right-handed helix. The structure could serve as a model for the design of antisense oligonucleotides resistant to nucleases and capable of hybridising to natural DNAs and RNAs.

[1]  H. Urata.  [Effect of chirality of ribose on nucleic acid structure and function]. , 1999, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[2]  D. Pisetsky.  The influence of base sequence on the immunostimulatory properties of DNA , 1999, Immunologic research.

[3]  R. Maroun,et al.  Comparative structural analysis by [1H,31P]-NMR and restrained molecular dynamics of two DNA hairpins from a strong DNA topoisomerase II cleavage site. , 1998, Journal of molecular biology.

[4]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[5]  A. Lane,et al.  Comparison of the solution structures of intramolecular DNA triple helices containing adjacent and non-adjacent CG.C+ triplets. , 1998, Nucleic acids research.

[6]  T. Klimkait,et al.  TAR-RNA binding by HIV-1 Tat protein is selectively inhibited by its L-enantiomer. , 1998, Nucleic acids research.

[7]  H. Kalbitzer,et al.  Protein NMR Spectroscopy. Principles and Practice , 1997 .

[8]  A T Brünger,et al.  Torsion-angle molecular dynamics as a new efficient tool for NMR structure calculation. , 1997, Journal of magnetic resonance.

[9]  V. Erdmann,et al.  Mirror-image RNA that binds D-adenosine , 1996, Nature Biotechnology.

[10]  Volker A. Erdmann,et al.  Mirror-design of L-oligonucleotide ligands binding to L-arginine , 1996, Nature Biotechnology.

[11]  Gabriele Varani,et al.  NMR investigation of RNA structure , 1996 .

[12]  A. Wang,et al.  Synthesis, structure and thermodynamic properties of 8-methylguanine-containing oligonucleotides: Z-DNA under physiological salt conditions. , 1996, Nucleic acids research.

[13]  G. Varani,et al.  Structure of the P1 helix from group I self-splicing introns. , 1995, Journal of molecular biology.

[14]  D. Gorenstein.  Conformation and Dynamics of DNA and Protein-DNA Complexes by 31P NMR , 1994 .

[15]  P. A. Giannaris,et al.  Antisense L/D-oligodeoxynucleotide chimeras: nuclease stability, base-pairing properties, and activity at directing ribonuclease H. , 1994, Biochemistry.

[16]  L. Tondelli,et al.  Effects of the introduction of L-nucleotides into DNA. Solution structure of the heterochiral duplex d(G-C-G-(L)T-G-C-G).d(C-G-C-A-C-G-C) studied by NMR spectroscopy. , 1994, Biochemistry.

[17]  C. Hilbers,et al.  L-DNAs as potential antimessenger oligonucleotides: a reassessment. , 1993, Nucleic acids research.

[18]  Yoshiaki Ueda,et al.  Synthesis and properties of mirror-image DNA , 1992, Nucleic Acids Res..

[19]  G. Varani,et al.  Carbon assignments and heteronuclear coupling constants for an RNA oligonucleotide from natural abundance carbon-13-proton correlated experiments , 1991 .

[20]  Christian Griesinger,et al.  Clean TOCSY for proton spin system identification in macromolecules , 1988 .

[21]  A. Bax,et al.  Assignment of the 31P and 1H resonances in oligonucleotides by two‐dimensional NMR spectroscopy , 1986, FEBS letters.

[22]  G. A. van der Marel,et al.  The B and Z forms of the d(m5C-G)3 and d(br5C-G)3 hexamers in solution. A 300-MHz and 500-MHz two-dimensional NMR study. , 1986, European journal of biochemistry.

[23]  A. Rich,et al.  A one- and two-dimensional NMR study of the B to Z transition of (m5dC-dG)3 in methanolic solution. , 1984, Nucleic acids research.

[24]  S. Stirdivant,et al.  Effects of 5 cytosine methylation on the B-Z transition in DNA restriction fragments and recombinant plasmids. , 1983, Journal of molecular biology.

[25]  K. Wüthrich,et al.  Application of phase sensitive two-dimensional correlated spectroscopy (COSY) for measurements of 1H-1H spin-spin coupling constants in proteins. , 1983, Biochemical and biophysical research communications.