3q61: Difference between revisions

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[[Image:3q61.jpg|left|200px]]
==3'-Fluoro Hexitol Nucleic Acid DNA Structure==
<StructureSection load='3q61' size='340' side='right' caption='[[3q61]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3q61]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q61 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3Q61 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=F3H:1,5-ANHYDRO-2,3-DIDEOXY-3-FLUORO-2-(5-METHYL-2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1(2H)-YL)-6-O-PHOSPHONO-D-ALTRITOL'>F3H</scene></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3q61 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q61 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3q61 RCSB], [http://www.ebi.ac.uk/pdbsum/3q61 PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The synthesis, biophysical, structural, and biological properties of both isomers of 3'-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides are reported. Synthesis of the FHNA and Ara-FHNA thymine phosphoramidites was efficiently accomplished starting from known sugar precursors. Optimal RNA affinities were observed with a 3'-fluorine atom and nucleobase in a trans-diaxial orientation. The Ara-FHNA analog with an equatorial fluorine was found to be destabilizing. However, the magnitude of destabilization was sequence-dependent. Thus, the loss of stability is sharply reduced when Ara-FHNA residues were inserted at pyrimidine-purine (Py-Pu) steps compared to placement within a stretch of pyrimidines (Py-Py). Crystal structures of A-type DNA duplexes modified with either monomer provide a rationalization for the opposing stability effects and point to a steric origin of the destabilization caused by the Ara-FHNA analog. The sequence dependent effect can be explained by the formation of an internucleotide C-F...H-C pseudo hydrogen bond between F3' of Ara-FHNA and C8-H of the nucleobase from the 3'-adjacent adenosine that is absent at Py-Py steps. In animal experiments, FHNA-modified antisense oligonucleotides formulated in saline showed a potent downregulation of gene expression in liver tissue without producing hepatotoxicity. Our data establish FHNA as a useful modification for antisense therapeutics and also confirm the stabilizing influence of F(Py)...H-C(Pu) pseudo hydrogen bonds in nucleic acid structures.


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Synthesis, improved antisense activity and structural rationale for the divergent RNA affinities of 3'-fluoro hexitol nucleic acid (FHNA and Ara-FHNA) modified oligonucleotides.,Egli M, Pallan PS, Allerson CR, Prakash TP, Berdeja A, Yu J, Lee S, Watt A, Gaus H, Bhat B, Swayze EE, Seth PP J Am Chem Soc. 2011 Oct 19;133(41):16642-9. Epub 2011 Sep 22. PMID:21919455<ref>PMID:21919455</ref>
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{{STRUCTURE_3q61|  PDB=3q61  |  SCENE=  }}


===3'-Fluoro Hexitol Nucleic Acid DNA Structure===
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
 
</div>
 
== References ==
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{{ABSTRACT_PUBMED_21919455}}
 
==About this Structure==
[[3q61]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q61 OCA].
 
==Reference==
<ref group="xtra">PMID:021919455</ref><references group="xtra"/>
[[Category: Allerson, C R.]]
[[Category: Allerson, C R.]]
[[Category: Berdeja, A.]]
[[Category: Berdeja, A.]]
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