X-ray crystal structure of a locked nucleic acid (LNA) duplex composed of a palindromic 10-mer DNA strand containing one LNA thymine monomer

Locked nucleic acid (LNA), a recently introduced nucleic acid analogue with a bicyclic 2′-O,4′-C-methylene linked furanose sugar, exhibits enhanced affinities for DNA and RNA relative to the corresponding oligodeoxyribonucleotides and oligoribonucleotides; we report the first crystal structure of an LNA unit incorporated in an oligonucleotide duplex. The structure at 1.4 A resolution of the DNA–LNA decamer duplex with one LNA thymine monomer per strand provides a detailed view of the conformation and hydration of locked nucleic acid residues in a duplex A-form.

[1]  J. Wengel,et al.  Solution structure of an LNA hybridized to DNA: NMR study of the d(CT(L)GCT(L)T(L)CT(L)GC):d(GCAGAAGCAG) duplex containing four locked nucleotides. , 2000, Bioconjugate chemistry.

[2]  J. Wengel,et al.  The solution structure of a locked nucleic acid (LNA) hybridized to DNA. , 1999, Journal of biomolecular structure & dynamics.

[3]  J. Wengel.  Synthesis of 3‘-C- and 4‘-C-Branched Oligodeoxynucleotides and the Development of Locked Nucleic Acid (LNA) , 1999 .

[4]  Y. Hari,et al.  Stability and structural features of the duplexes containing nucleoside analogues with a fixed N-type conformation, 2'-O,4'- C-methyleneribonucleosides , 1998 .

[5]  Poul Nielsen,et al.  LNA (Locked Nucleic Acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition , 1998 .

[6]  R. Adamiak,et al.  Crystal structure of 2'-O-Me(CGCGCG)2, an RNA duplex at 1.30 A resolution. Hydration pattern of 2'-O-methylated RNA. , 1997, Nucleic acids research.

[7]  J. Navaza,et al.  AMoRe: an automated package for molecular replacement , 1994 .

[8]  A. Rich,et al.  Conformational influence of the ribose 2'-hydroxyl group: crystal structures of DNA-RNA chimeric duplexes , 1993 .

[9]  A. Brunger.  Free R value: a novel statistical quantity for assessing the accuracy of crystal structures. , 1992 .

[10]  M. Sundaralingam,et al.  Conformational analysis of the sugar ring in nucleosides and nucleotides. A new description using the concept of pseudorotation. , 1972, Journal of the American Chemical Society.

[11]  J. Wengel,et al.  The conformations of locked nucleic acids (LNA) , 2000, Journal of molecular recognition : JMR.

[12]  M. Egli,et al.  Consequences of Replacing the DNA 3‘-Oxygen by an Amino Group: High-Resolution Crystal Structure of a Fully Modified N3‘ → P5‘ Phosphoramidate DNA Dodecamer Duplex† , 1998 .

[13]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.