411d
From Proteopedia
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[[Image:411d.gif|left|200px]] | [[Image:411d.gif|left|200px]] | ||
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| - | + | {{STRUCTURE_411d| PDB=411d | SCENE= }} | |
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'''DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE''' | '''DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE''' | ||
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==About this Structure== | ==About this Structure== | ||
| - | + | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=411D OCA]. | |
==Reference== | ==Reference== | ||
Correlating structure and stability of DNA duplexes with incorporated 2'-O-modified RNA analogues., Tereshko V, Portmann S, Tay EC, Martin P, Natt F, Altmann KH, Egli M, Biochemistry. 1998 Jul 28;37(30):10626-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9692952 9692952] | Correlating structure and stability of DNA duplexes with incorporated 2'-O-modified RNA analogues., Tereshko V, Portmann S, Tay EC, Martin P, Natt F, Altmann KH, Egli M, Biochemistry. 1998 Jul 28;37(30):10626-34. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9692952 9692952] | ||
| - | [[Category: Protein complex]] | ||
[[Category: Altmann, K H.]] | [[Category: Altmann, K H.]] | ||
[[Category: Egli, M.]] | [[Category: Egli, M.]] | ||
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[[Category: Tay, E C.]] | [[Category: Tay, E C.]] | ||
[[Category: Tereshko, V.]] | [[Category: Tereshko, V.]] | ||
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Revision as of 19:16, 4 May 2008
DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE
Overview
Chemically modified nucleic acids are currently being evaluated as potential antisense compounds for therapeutic applications. 2'-O-Ethylene glycol substituted oligoribonucleotides are second-generation antisense inhibitors of gene expression with promising features for in vivo use. Relative to DNA, they display improved RNA affinity and higher nuclease resistance. Moreover, chimeric oligonucleotides with 2'-O-methoxyethyl ribonucleoside wings and a central DNA phosphorothioate window have been shown to effectively reduce the growth of tumors in animal models at low doses. Using X-ray crystallography, we have determined the structures of three A-form DNA duplexes containing the following 2'-O-modified ribothymidine building blocks: 2'-O-methoxyethyl ribo-T, 2'-O-methyl[tri(oxyethyl)] ribo-T, and 2'-O-ethoxymethylene ribo-T. In contrast to 2'-O-ethylene glycol substituents, the presence of a 2'-O-ethoxymethylene group leads to slightly reduced RNA affinity of the corresponding oligonucleotides. The three structures allow a qualitative rationalization of the differing stabilities of duplexes between oligonucleotides comprising these types of 2'-O-modified ribonucleotides and complementary RNAs. The stabilizing 2'-O-ethylene glycol substituents are conformationally preorganized for the duplex state. Thus, the presence of one or several ethylene glycol moieties may reduce the conformational space of the substituents in an oligonucleotide single strand. In addition, most of these preferred conformations appear to be compatible with the minor groove topology in an A-type duplex. Factors that contribute to the conformational rigidity of the 2'-O-substituents are anomeric and gauche effects, electrostatic interactions between backbone and substituent, and bound water molecules.
About this Structure
Full crystallographic information is available from OCA.
Reference
Correlating structure and stability of DNA duplexes with incorporated 2'-O-modified RNA analogues., Tereshko V, Portmann S, Tay EC, Martin P, Natt F, Altmann KH, Egli M, Biochemistry. 1998 Jul 28;37(30):10626-34. PMID:9692952 Page seeded by OCA on Sun May 4 22:16:31 2008
