4a6c: Difference between revisions

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-[[Image:4a6c.jpg|left|200px]]
+==Stereoselective Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Lactam Based HIV-1 Protease Inhibitors==
+<StructureSection load='4a6c' size='340' side='right' caption='[[4a6c]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4a6c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A6C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A6C FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=QG9:METHYL+((S)-1-(2-(3-((3S,4S)-3-BENZYL-4-HYDROXY-1-((1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL)-2-OXOPYRROLIDIN-3-YL)PROPYL)-2-(4-(PYRIDIN-4-YL)BENZYL)HYDRAZINYL)-3,3-DIMETHYL-1-OXOBUTAN-2-YL)CARBAMATE'>QG9</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gno|1gno]], [[2cem|2cem]], [[2cej|2cej]], [[1zpa|1zpa]], [[1wbk|1wbk]], [[1wbm|1wbm]], [[4a4q|4a4q]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] </span></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=4a6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a6c OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a6c RCSB], [http://www.ebi.ac.uk/pdbsum/4a6c PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+In an effort to identify a new class of druglike HIV-1 protease inhibitors, four different stereopure beta-hydroxy gamma-lactam-containing inhibitors have been synthesized, biologically evaluated, and cocrystallized. The impact of the tether length of the central spacer (two or three carbons) was also investigated. A compound with a shorter tether and (3R,4S) absolute configuration exhibited high activity with a K(i) of 2.1 nM and an EC(50) of 0.64 muM. Further optimization by decoration of the P1' side chain furnished an even more potent HIV-1 protease inhibitor (K(i) = 0.8 nM, EC(50) = 0.04 muM). According to X-ray analysis, the new class of inhibitors did not fully succeed in forming two symmetric hydrogen bonds to the catalytic aspartates. The crystal structures of the complexes further explain the difference in potency between the shorter inhibitors (two-carbon spacer) and the longer inhibitors (three-carbon spacer).
-<!--
+Synthesis, X-ray analysis, and biological evaluation of a new class of stereopure lactam-based HIV-1 protease inhibitors.,Wu X, Ohrngren P, Joshi AA, Trejos A, Persson M, Arvela RK, Wallberg H, Vrang L, Rosenquist A, Samuelsson BB, Unge J, Larhed M J Med Chem. 2012 Mar 22;55(6):2724-36. Epub 2012 Mar 13. PMID:22376008<ref>PMID:22376008</ref>
-The line below this paragraph, containing "STRUCTURE_4a6c", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
--->
-{{STRUCTURE_4a6c|  PDB=4a6c  |  SCENE=  }}
-===Stereoselective Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Lactam Based HIV-1 Protease Inhibitors===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+== References ==
-<!--
+<references/>
-The line below this paragraph, {{ABSTRACT_PUBMED_22376008}}, adds the Publication Abstract to the page
+__TOC__
-(as it appears on PubMed at http://www.pubmed.gov), where 22376008 is the PubMed ID number.
+</StructureSection>
--->
-{{ABSTRACT_PUBMED_22376008}}
-==About this Structure==
-[[4a6c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus Human immunodeficiency virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A6C OCA].
-==Reference==
-<ref group="xtra">PMID:022376008</ref><references group="xtra"/>
 [[Category: HIV-1 retropepsin]]
 [[Category: Human immunodeficiency virus]]
-[[Category: Arvela, R K.]]
+[[Category: Arvela, R K]]
-[[Category: Joshi, A A.]]
+[[Category: Joshi, A A]]
-[[Category: Larhed, M.]]
+[[Category: Larhed, M]]
-[[Category: Ohrngren, P.]]
+[[Category: Ohrngren, P]]
-[[Category: Persson, M.]]
+[[Category: Persson, M]]
-[[Category: Rosenquist, A.]]
+[[Category: Rosenquist, A]]
-[[Category: Samuelsson, B B.]]
+[[Category: Samuelsson, B B]]
-[[Category: Trejos, A.]]
+[[Category: Trejos, A]]
-[[Category: Unge, J.]]
+[[Category: Unge, J]]
-[[Category: Vrang, L.]]
+[[Category: Vrang, L]]
-[[Category: Wallberg, H.]]
+[[Category: Wallberg, H]]
-[[Category: Wu, X.]]
+[[Category: Wu, X]]
 [[Category: Gamma-butyrol-lactam]]
 [[Category: Hydrolase]]