5dek - Revision history

OCA at 12:24, 6 March 2024

2024-03-06T12:24:07Z

←Older revision		Revision as of 12:24, 6 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[5dek]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DEK FirstGlance]. <br>		<table><tr><td colspan='2'>[[5dek]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DEK FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.993Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</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=5dek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dek OCA], [https://pdbe.org/5dek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dek RCSB], [https://www.ebi.ac.uk/pdbsum/5dek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dek ProSAT]</span></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=5dek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dek OCA], [https://pdbe.org/5dek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dek RCSB], [https://www.ebi.ac.uk/pdbsum/5dek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dek ProSAT]</span></td></tr>
	</table>		</table>
-	<div style="background-color:#fffaf0;">
-	== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 5dek" style="background-color:#fffaf0;"></div>
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 10:32, 21 June 2023

2023-06-21T10:32:21Z

←Older revision		Revision as of 10:32, 21 June 2023
Line 3:		Line 3:
	<StructureSection load='5dek' size='340' side='right'caption='[[5dek]], [[Resolution\|resolution]] 1.99Å' scene=''>		<StructureSection load='5dek' size='340' side='right'caption='[[5dek]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dek]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEK OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5DEK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dek]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DEK FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</scene></td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5der\|5der]]</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=5dek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dek OCA], [https://pdbe.org/5dek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dek RCSB], [https://www.ebi.ac.uk/pdbsum/5dek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dek ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5dek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dek OCA], [~~http~~://pdbe.org/5dek PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5dek RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5dek PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5dek ProSAT]</span></td></tr>	+
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 22:		Line 21:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Egli, M~~]]	+	[[Category: Synthetic construct]]
-	[[Category: ~~Harp, J~~ M]]	+	[[Category: Egli M]]
-	[[Category: ~~Oligonucleotide]]~~	+	[[Category: Harp JM]]
-	~~[[Category: Rna~~]]	+

OCA at 08:00, 8 April 2020

2020-04-08T08:00:52Z

←Older revision		Revision as of 08:00, 8 April 2020
Line 1:		Line 1:

	==RNA octamer containing dT==		==RNA octamer containing dT==
-	<StructureSection load='5dek' size='340' side='right' caption='[[5dek]], [[Resolution\|resolution]] 1.99Å' scene=''>	+	<StructureSection load='5dek' size='340' side='right'caption='[[5dek]], [[Resolution\|resolution]] 1.99Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5dek]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEK OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5DEK FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5dek]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5DEK 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>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NCO:COBALT+HEXAMMINE(III)'>NCO</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5der\|5der]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5der\|5der]]</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=5dek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dek OCA], [http://pdbe.org/5dek PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dek RCSB], [http://www.ebi.ac.uk/pdbsum/5dek PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dek ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5dek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dek OCA], [http://pdbe.org/5dek PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dek RCSB], [http://www.ebi.ac.uk/pdbsum/5dek PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dek ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 21:		Line 21:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Large Structures]]
	[[Category: Egli, M]]		[[Category: Egli, M]]
	[[Category: Harp, J M]]		[[Category: Harp, J M]]
	[[Category: Oligonucleotide]]		[[Category: Oligonucleotide]]
	[[Category: Rna]]		[[Category: Rna]]

OCA at 15:15, 26 July 2016

2016-07-26T15:15:01Z

←Older revision		Revision as of 15:15, 26 July 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5dek is ~~ON HOLD until Paper~~ Publication	+	==RNA octamer containing dT==
		+	<StructureSection load='5dek' size='340' side='right' caption='[[5dek]], [[Resolution\|resolution]] 1.99Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5dek]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DEK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DEK 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='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5der\|5der]]</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=5dek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dek OCA], [http://pdbe.org/5dek PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dek RCSB], [http://www.ebi.ac.uk/pdbsum/5dek PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5dek ProSAT]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== 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.

-	~~Authors: Harp~~, J.M., Egli, M.	+	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>

-	~~Description: RNA octamer containing dT~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category: Unreleased Structures]]~~	+	</div>
-	~~[[Category~~: ~~Harp, J.M]]~~	+	<div class="pdbe-citations 5dek" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Egli, M]]		[[Category: Egli, M]]
		+	[[Category: Harp, J M]]
		+	[[Category: Oligonucleotide]]
		+	[[Category: Rna]]

OCA at 05:07, 14 July 2016

2016-07-14T05:07:31Z

←Older revision		Revision as of 05:07, 14 July 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5dek is ON HOLD	+	The entry 5dek is ON HOLD until Paper Publication

	Authors: Harp, J.M., Egli, M.		Authors: Harp, J.M., Egli, M.

OCA: Protected "5dek" [edit=sysop:move=sysop]

2015-09-02T11:33:04Z

Protected "5dek" [edit=sysop:move=sysop]

←Older revision

Revision as of 11:33, 2 September 2015

OCA: New page: '''Unreleased structure''' The entry 5dek is ON HOLD Authors: Harp, J.M., Egli, M. Description: RNA octamer containing dT Category: Unreleased Structures Category: Harp, J.M [[...

2015-09-02T11:33:02Z

New page: '''Unreleased structure''' The entry 5dek is ON HOLD Authors: Harp, J.M., Egli, M. Description: RNA octamer containing dT Category: Unreleased Structures Category: Harp, J.M [[...

New page

'''Unreleased structure'''

The entry 5dek is ON HOLD

Authors: Harp, J.M., Egli, M.

Description: RNA octamer containing dT
[[Category: Unreleased Structures]]
[[Category: Harp, J.M]]
[[Category: Egli, M]]