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X-ray Crystal Structure of a Locked Nucleic Acid (LNA) Duplex Composed of a Palindromic 10-mer DNA Strand Containing One LNA Thymine Monomer

Journal Article · · Chem. Commun.
OSTI ID:1006372
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 {angstrom} 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. Our study provides a first look at the conformational properties of LNA in a crystal structure at relatively high resolution. The main characteristics of the structure are the standard A-type conformation induced by LNA residues and the capacity of the 2'-oxygen that is part of the bicyclic sugar framework to engage in a least two hydrogen bonds to water molecules. Circular dichroism spectra (CD) of LNA-LNA duplexes in solution indicated that such duplexes appear to adopt a conformation that closely resembles the A-form geometry of RNA-RNA duplexes. However, these spectra also manifested subtle differences between the two species (data not shown). The present analysis of a duplex with only a single LNA residue per strand does not provide any insight into potential conformational differences between LNA and RNA duplexes. Attempts to determine a crystal structure of a completely modified LNA-LNA duplex are underway.
Research Organization:
Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Organization:
USDOE
OSTI ID:
1006372
Journal Information:
Chem. Commun., Journal Name: Chem. Commun. Journal Issue: 2001 Vol. 7; ISSN 1359-7345
Country of Publication:
United States
Language:
ENGLISH