1D7Z

CRYSTAL STRUCTURE OF A HEXITOL NUCLEIC ACID (HNA) DUPLEX AT 2.2 A RESOLUTION

Summary for 1D7Z

• Entry DOI: 10.2210/pdb1d7z/pdb
• Descriptor: 5'-H(*(6HG)P*(6HT)P*(6HG)P*(6HT)P*(6HA)P*(6HC)P*(6HA)P*(6HC))-3' (2 entities in total)
• Functional Keywords: hexitol nucleic acid, dna analogue, double helix, dna
• Total number of polymer chains: 1
• Total formula weight: 2538.83

Authors

Declercq, R.,Van Meervelt, L. (deposition date: 1999-10-21, release date: 2002-06-28, Last modification date: 2024-02-07)

Primary citation

Declercq, R.,Van Aerschot, A.,Read, R.J.,Herdewijn, P.,Van Meervelt, L.
Crystal structure of double helical hexitol nucleic acids.
J.Am.Chem.Soc., 124:928-933, 2002

PubMed Abstract: A huge variety of chemically modified oligonucleotide derivatives has been synthesized for possible antisense applications. One such derivative, hexitol nucleic acid (HNA), is a DNA analogue containing the standard nucleoside bases, but with a phosphorylated 1',5'-anhydrohexitol backbone. Hexitol nucleic acids are some of the strongest hybridizing antisense compounds presently known, but HNA duplexes are even more stable. We present here the first high-resolution structure of a double helical nucleic acid with all sugars being hexitols. Although designed to have a restricted conformational flexibility, the hexitol oligomer h(GTGTACAC) is able to crystallize in two different double helical conformations. Both structures display a high x-displacement, normal Watson-Crick base pairing, similar base stacking patterns, and a very deep major groove together with a minor groove with increased hydrophobicity. One of the conformations displays a major groove which is wide enough to accommodate a second HNA double helix resulting in the formation of a double helix of HNA double helices. Both structures show most similarities with the A-type helical structure, the anhydrohexitol chair conformation thereby acting as a good mimic for the furanose C3'-endo conformation observed in RNA. As compared to the quasi-linear structure of homo-DNA, the axial position of the base in HNA allows efficient base stacking and hence double helix formation.

PubMed: 11829600
DOI: 10.1021/ja016570w

Experimental method

X-RAY DIFFRACTION (2.21 Å)