411d: Difference between revisions
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'''DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE''' | {{Structure | ||
|PDB= 411d |SIZE=350|CAPTION= <scene name='initialview01'>411d</scene>, resolution 1.930Å | |||
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'''DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
411D is a [ | 411D is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. 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:// | 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: Protein complex]] | ||
[[Category: Altmann, K H.]] | [[Category: Altmann, K H.]] | ||
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[[Category: duplex [5'-d(gcgta+tacgc)]2 with incorporated 2'-o-methoxyethyl ribonucleoside]] | [[Category: duplex [5'-d(gcgta+tacgc)]2 with incorporated 2'-o-methoxyethyl ribonucleoside]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 19:07:58 2008'' | ||
Revision as of 20:07, 20 March 2008
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DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE
OverviewOverview
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 StructureAbout this Structure
411D is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
ReferenceReference
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 [[Category: duplex [5'-d(gcgta+tacgc)]2 with incorporated 2'-o-methoxyethyl ribonucleoside]]
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