5d8t

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CBV:5-BROMOCYTIDINE+5-(DIHYDROGEN+PHOSPHATE)'>CBV</scene>, <scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</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>

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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 ==

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