View source for 3oz4


==R-Methyl Carbocyclic LNA==
<StructureSection load='3oz4' size='340' side='right'caption='[[3oz4]], [[Resolution|resolution]] 1.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3oz4]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OZ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OZ4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=URX:[(1R,3R,4R,5R,7S)-3-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)-7-HYDROXY-5-METHYL-2-OXABICYCLO[2.2.1]HEPT-1-YL]METHYL+DIHYDROGEN+PHOSPHATE'>URX</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oz4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oz4 OCA], [https://pdbe.org/3oz4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oz4 RCSB], [https://www.ebi.ac.uk/pdbsum/3oz4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oz4 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We show for the first time that it is possible to obtain LNA-like (Locked Nucleic Acid 1) binding affinity and biological activity with carbocyclic LNA (cLNA) analogs by replacing the 2'-oxygen atom in LNA with an exocyclic methylene group. Synthesis of the methylene-cLNA nucleoside was accomplished by an intramolecular cyclization reaction between a radical at the 2'-position and a propynyl group at the C-4' position. Only methylene-cLNA modified oligonucleotides showed similar thermal stability and mismatch discrimination properties for complementary nucleic acids as LNA. In contrast, the close structurally related methyl-cLNA analogs showed diminished hybridization properties. Analysis of crystal structures of cLNA modified self-complementary DNA decamer duplexes revealed that the methylene group participates in a tight interaction with a 2'-deoxyribose residue of the 5'-terminal G of a neighboring duplex, resulting in the formation of a CH...O type hydrogen bond. This indicates that the methylene group retains a negative polarization at the edge of the minor groove in the absence of a hydrophilic 2'-substituent and provides a rationale for the superior thermal stability of this modification. In animal experiments, methylene-cLNA antisense oligonucleotides (ASOs) showed similar in vivo activity but reduced toxicity as compared to LNA ASOs. Our work highlights the interchangeable role of oxygen and unsaturated moieties in nucleic acid structure and emphasizes greater use of this bioisostere to improve the properties of nucleic acids for therapeutic and diagnostic applications.

An exocyclic methylene group acts as a bioisostere of the 2'-oxygen atom in LNA.,Seth PP, Allerson CR, Berdeja A, Siwkowski A, Pallan PS, Gaus H, Prakash TP, Watt AT, Egli M, Swayze EE J Am Chem Soc. 2010 Oct 27;132(42):14942-50. PMID:20886816<ref>PMID:20886816</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3oz4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Allerson CA]]
[[Category: Berdeja A]]
[[Category: Egli M]]
[[Category: Gaus H]]
[[Category: Pallan PS]]
[[Category: Prakash TP]]
[[Category: Seth PR]]
[[Category: Siwkowski A]]
[[Category: Swayze EE]]
[[Category: Watt AT]]