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4ewo

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[[Image:4ewo.jpg|left|200px]]
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==Design and synthesis of potent hydroxyethylamine (hea) bace-1 inhibitors==
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<StructureSection load='4ewo' size='340' side='right' caption='[[4ewo]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4ewo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EWO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EWO FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=996:N-[(2S,3R)-4-{[(4S)-2-(2,2-DIMETHYLPROPYL)-6,6-DIMETHYL-4,5,6,7-TETRAHYDRO-2H-INDAZOL-4-YL]AMINO}-3-HYDROXY-1-PHENYLBUTAN-2-YL]ACETAMIDE'>996</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4exg|4exg]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></td></tr>
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<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=4ewo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ewo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ewo RCSB], [http://www.ebi.ac.uk/pdbsum/4ewo PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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A set of low molecular weight compounds containing a hydroxyethylamine (HEA) core structure with different prime side alkyl substituted 4,5,6,7-tetrahydrobenzazoles and one 4,5,6,7-tetrahydropyridinoazole was synthesized. Striking differences were observed on potencies in the BACE-1 enzymatic and cellular assays depending on the nature of the heteroatoms in the bicyclic ring, from the low active compound 4 to inhibitor 6, displaying BACE-1 IC(50) values of 44 nM (enzyme assay) and 65 nM (cell-based assay).
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{{STRUCTURE_4ewo| PDB=4ewo | SCENE= }}
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Design and synthesis of potent hydroxyethylamine (HEA) BACE-1 inhibitors carrying prime side 4,5,6,7-tetrahydrobenzazole and 4,5,6,7-tetrahydropyridinoazole templates.,Sund C, Belda O, Borkakoti N, Lindberg J, Derbyshire D, Vrang L, Hamelink E, Ahgren C, Woestenenk E, Wikstrom K, Eneroth A, Lindstrom E, Kalayanov G Bioorg Med Chem Lett. 2012 Nov 1;22(21):6721-7. doi: 10.1016/j.bmcl.2012.08.097. , Epub 2012 Sep 5. PMID:23010268<ref>PMID:23010268</ref>
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===Design and synthesis of potent hydroxyethylamine (hea) bace-1 inhibitors===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_23010268}}
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==See Also==
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*[[Beta secretase|Beta secretase]]
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==About this Structure==
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== References ==
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[[4ewo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EWO OCA].
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<references/>
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[[Category: Homo sapiens]]
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__TOC__
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</StructureSection>
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[[Category: Human]]
[[Category: Memapsin 2]]
[[Category: Memapsin 2]]
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[[Category: Borkakoti, N.]]
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[[Category: Borkakoti, N]]
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[[Category: Derbyshire, D.]]
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[[Category: Derbyshire, D]]
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[[Category: Lindberg, J.]]
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[[Category: Lindberg, J]]
[[Category: Aspartyl protease]]
[[Category: Aspartyl protease]]
[[Category: Bace]]
[[Category: Bace]]

Revision as of 17:23, 9 December 2014

Design and synthesis of potent hydroxyethylamine (hea) bace-1 inhibitors

4ewo, resolution 1.80Å

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