5d8t

<StructureSection load='5d8t' size='340' side='right' caption='[[5d8t]], [[Resolution|resolution]] 1.20&Aring;' scene=''>

<table><tr><td colspan='2'>[[5d8t]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D8T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D8T FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</scene></td></tr>

<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CBV:5-BROMOCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>CBV</scene>, <scene name='pdbligand=U5M:1-(2,6-DIDEOXY-2-FLUORO-5-O-PHOSPHONO-ALPHA-L-TALOFURANOSYL)PYRIMIDINE-2,4(1H,3H)-DIONE'>U5M</scene></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5d8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d8t OCA], [http://pdbe.org/5d8t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d8t RCSB], [http://www.ebi.ac.uk/pdbsum/5d8t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d8t ProSAT]</span></td></tr>

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== Publication Abstract from PubMed ==

Although judicious use of chemical modifications has contributed to the success of nucleic acid therapeutics, poor systemic stability remains a major hurdle. The introduction of functional groups around the phosphate backbone can enhance the nuclease resistance of oligonucleotides (ONs). Here, we report the synthesis of enantiomerically pure (R)- and (S)-5'-C-methyl (C5'-Me) substituted nucleosides and their incorporation into ONs. These modifications generally resulted in a decrease in thermal stability of oligonucleotide (ON) duplexes in a manner dependent on the stereoconfiguration at C5' with greater destabilization characteristic of (R)-epimers. Enhanced stability against snake venom phosphodiesterase resulted from modification of the 3'-end of an ON with either (R)- or (S)-C5'-Me nucleotides. The (S)-isomers with different 2'-substituents provided greater resistance against 3'-exonucleases than the corresponding (R)-isomers. Crystal structure analyses of RNA octamers with (R)- or (S)-5'-C-methyl-2'-deoxy-2'-fluorouridine [(R)- or (S)-C5'-Me-2'-FU, respectively] revealed that the stereochemical orientation of the C5'-Me and the steric effects that emanate from the alkyl substitution are the dominant determinants of thermal stability and are likely molecular origins of resistance against nucleases. X-ray and NMR structural analyses showed that the (S)-C5'-Me epimers are spatially and structurally more similar to their natural 5' nonmethylated counterparts than the corresponding (R)-epimers.

Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5'-C-Methyl Pyrimidine-Modified Oligonucleotides.,Kel In AV, Zlatev I, Harp J, Jayaraman M, Bisbe A, O Shea J, Taneja N, Manoharan RM, Khan S, Charisse K, Maier MA, Egli M, Rajeev KG, Manoharan M J Org Chem. 2016 Mar 18;81(6):2261-79. doi: 10.1021/acs.joc.5b02375. Epub 2016, Mar 4. PMID:26940174<ref>PMID:26940174</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Egli, M]]

[[Category: Harp, J M]]

[[Category: Modified base]]

[[Category: Rna]]