|
|
| (10 intermediate revisions by the same user not shown) |
| Line 1: |
Line 1: |
| [[Image:411d.gif|left|200px]]<br /><applet load="411d" size="350" color="white" frame="true" align="right" spinBox="true"
| |
| caption="411d, resolution 1.930Å" />
| |
| '''DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE'''<br />
| |
|
| |
|
| ==Overview== | | ==DUPLEX [5'-D(GCGTA+TACGC)]2 WITH INCORPORATED 2'-O-METHOXYETHYL RIBONUCLEOSIDE== |
| 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.
| | <StructureSection load='411d' size='340' side='right'caption='[[411d]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | | == Structural highlights == |
| ==About this Structure== | | <table><tr><td colspan='2'>[[411d]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=411D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=411D FirstGlance]. <br> |
| 411D is a [http://en.wikipedia.org/wiki/Protein_complex 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].
| | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93Å</td></tr> |
| | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=T39:2-O-METHOXYETHYLENE+THYMIDINE+5-MONOPHOSPHATE'>T39</scene></td></tr> |
| ==Reference== | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=411d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=411d OCA], [https://pdbe.org/411d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=411d RCSB], [https://www.ebi.ac.uk/pdbsum/411d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=411d ProSAT]</span></td></tr> |
| 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://ispc.weizmann.ac.il//pmbin/getpm?pmid=9692952 9692952]
| | </table> |
| [[Category: Protein complex]] | | __TOC__ |
| [[Category: Altmann, K.H.]] | | </StructureSection> |
| [[Category: Egli, M.]] | | [[Category: Large Structures]] |
| [[Category: Martin, P.]] | | [[Category: Altmann KH]] |
| [[Category: Natt, F.]] | | [[Category: Egli M]] |
| [[Category: Portmann, S.]] | | [[Category: Martin P]] |
| [[Category: Tay, E.C.]] | | [[Category: Natt F]] |
| [[Category: Tereshko, V.]] | | [[Category: Portmann S]] |
| [[Category: duplex [5'-d(gcgta+tacgc)]2 with incorporated 2'-o-methoxyethyl ribonucleoside]]
| | [[Category: Tay EC]] |
| | | [[Category: Tereshko V]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 21:42:30 2008''
| |
