168d | pdb_0000168d

STABILIZING EFFECTS OF THE RNA 2'-SUBSTITUENT: CRYSTAL STRUCTURE OF AN OLIGODEOXYNUCLEOTIDE DUPLEX CONTAINING 2'-O-METHYLATED ADENOSINES

spinqualitylabelsall models 168d, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 168d is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: A2M Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed BACKGROUND: The stability of hybrids of 2'-O-methyl-ribonucleotides with complementary RNA is considerably higher than that of the corresponding DNA.RNA duplexes. The 2'-O-modified ribonucleotides are thus an attractive class of compounds for antisense applications. Understanding how these substituents stabilize the structure of the hybrid duplex may be important in the design of ribonucleotides with novel properties. RESULTS: The crystal structure of a dimer of the self-complementary DNA strand d(GCGT)O2'mer(A)d(TACGC), which has a 2'-O-methylated ribonucleotide incorporated at position 5, was determined at 2.1 A resolution. This strand forms a duplex with an overall A-type conformation; the methyl groups of the two modified adenosines point into the relatively wide minor groove. Both 2'-methoxy groups are hydrogen-bonded to solvent molecules. These results allowed us to build a model of a fully 2'-O-methylated RNA double helix. CONCLUSIONS: Insertion of 2'-O-modified RNA residues into a stretch of DNA can nucleate a local A-type conformation, in part because modification with a bulky residue at this position stabilizes a C3'-endo type sugar pucker. The increased stability of fully 2'-O-methylated RNA may result from hydrophobic interactions between substituents in the minor groove. As the 2'-O-methyl groups are directed into the minor groove, it may be worthwhile to introduce tailor-made 2'-O-substituents into RNA; it might be possible to design groups that both stabilize the hybrid duplexes and carry a nuclease function, further improving the efficacy of these modified RNAs in antisense applications. Stabilizing effects of the RNA 2'-substituent: crystal structure of an oligodeoxynucleotide duplex containing 2'-O-methylated adenosines.,Lubini P, Zurcher W, Egli M Chem Biol. 1994 Sep;1(1):39-45. PMID:9383369 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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