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[[Image: | ==HIV-1 PROTEASE INHIBITORS CONTAINING A TERTIARY ALCOHOL IN THE TRANSITION-STATE MIMIC WITH IMPROVED CELL-BASED ANTIVIRAL ACTIVITY== | ||
<StructureSection load='2wl0' size='340' side='right' caption='[[2wl0]], [[Resolution|resolution]] 1.90Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2wl0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Viruses Viruses]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WL0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WL0 FirstGlance]. <br> | |||
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5AH:METHYL+[(1S)-1-({2-[(3S)-3-BENZYL-3-HYDROXY-4-{[(1S,2R)-2-HYDROXY-2,3-DIHYDRO-1H-INDEN-1-YL]AMINO}-4-OXOBUTYL]-2-(4-PYRIDIN-2-YLBENZYL)HYDRAZINO}CARBONYL)-2,2-DIMETHYLPROPYL]CARBAMATE'>5AH</scene><br> | |||
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2vg7|2vg7]], [[1ajv|1ajv]], [[1har|1har]], [[1hps|1hps]], [[1t7k|1t7k]], [[1d4j|1d4j]], [[1r0a|1r0a]], [[1hpz|1hpz]], [[2vg6|2vg6]], [[1hqe|1hqe]], [[1qe1|1qe1]], [[1npa|1npa]], [[1ajx|1ajx]], [[1ebk|1ebk]], [[1tvr|1tvr]], [[1s6p|1s6p]], [[1ikv|1ikv]], [[1bqm|1bqm]], [[1w5y|1w5y]], [[1hos|1hos]], [[1ikw|1ikw]], [[1s6q|1s6q]], [[3hvt|3hvt]], [[1ec1|1ec1]], [[1ec0|1ec0]], [[1t05|1t05]], [[1rvq|1rvq]], [[1d4i|1d4i]], [[1meu|1meu]], [[1s9g|1s9g]], [[2be2|2be2]], [[1hnv|1hnv]], [[1rvr|1rvr]], [[1ikx|1ikx]], [[1w5w|1w5w]], [[1iky|1iky]], [[1qmc|1qmc]], [[1n6q|1n6q]], [[1d4h|1d4h]], [[1rvn|1rvn]], [[1hbv|1hbv]], [[1htf|1htf]], [[1rtd|1rtd]], [[1ec2|1ec2]], [[2hmi|2hmi]], [[1w5v|1w5v]], [[1sv5|1sv5]], [[2uy0|2uy0]], [[1hmv|1hmv]], [[2bbb|2bbb]], [[1s9e|1s9e]], [[1n5y|1n5y]], [[1dlo|1dlo]], [[2wkz|2wkz]], [[1heg|1heg]], [[1rvp|1rvp]], [[1rvl|1rvl]], [[1dw6|1dw6]], [[1eet|1eet]], [[1w5x|1w5x]], [[1yt9|1yt9]], [[2b6a|2b6a]], [[1htg|1htg]], [[1hvu|1hvu]], [[1ebw|1ebw]], [[1rdh|1rdh]], [[2ban|2ban]], [[1eby|1eby]], [[1j5o|1j5o]], [[1rvo|1rvo]], [[1hvp|1hvp]], [[1mes|1mes]], [[1ec3|1ec3]], [[1hef|1hef]], [[1hih|1hih]], [[1hni|1hni]], [[1tv6|1tv6]], [[1a9m|1a9m]], [[1ebz|1ebz]], [[2b5j|2b5j]], [[1hys|1hys]], [[1met|1met]], [[1t03|1t03]], [[1axa|1axa]], [[1mer|1mer]], [[1npw|1npw]], [[3tlh|3tlh]], [[1suq|1suq]], [[2uxz|2uxz]], [[1hvk|1hvk]], [[1sbg|1sbg]], [[1bqn|1bqn]], [[1uwb|1uwb]], [[2vg5|2vg5]], [[1rvm|1rvm]], [[1hte|1hte]], [[1hrh|1hrh]], [[1npv|1npv]], [[1hqu|1hqu]]</td></tr> | |||
<tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wl0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wl0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wl0 RCSB], [http://www.ebi.ac.uk/pdbsum/2wl0 PDBsum]</span></td></tr> | |||
<table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wl/2wl0_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
By a small modification in the core structure of the previously reported series of HIV-1 protease inhibitors that encompasses a tertiary alcohol as part of the transition-state mimicking scaffold, up to 56 times more potent compounds were obtained exhibiting EC(50) values down to 3 nM. Three of the inhibitors also displayed excellent activity against selected resistant isolates of HIV-1. The synthesis of 25 new and optically pure HIV-1 protease inhibitors is reported, along with methods for elongation of the inhibitor P1' side chain using microwave-accelerated, palladium-catalyzed cross-coupling reactions, the biological evaluation, and X-ray data obtained from one of the most potent analogues cocrystallized with both the wild type and the L63P, V82T, I84 V mutant of the HIV-1 protease. | |||
HIV-1 Protease Inhibitors with a Transition-State Mimic Comprising a Tertiary Alcohol: Improved Antiviral Activity in Cells.,Mahalingam AK, Axelsson L, Ekegren JK, Wannberg J, Kihlstrom J, Unge T, Wallberg H, Samuelsson B, Larhed M, Hallberg A J Med Chem. 2009 Dec 4. PMID:19961222<ref>PMID:19961222</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Virus protease|Virus protease]] | *[[Virus protease|Virus protease]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Viruses]] | [[Category: Viruses]] | ||
Revision as of 09:28, 29 September 2014
HIV-1 PROTEASE INHIBITORS CONTAINING A TERTIARY ALCOHOL IN THE TRANSITION-STATE MIMIC WITH IMPROVED CELL-BASED ANTIVIRAL ACTIVITYHIV-1 PROTEASE INHIBITORS CONTAINING A TERTIARY ALCOHOL IN THE TRANSITION-STATE MIMIC WITH IMPROVED CELL-BASED ANTIVIRAL ACTIVITY
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedBy a small modification in the core structure of the previously reported series of HIV-1 protease inhibitors that encompasses a tertiary alcohol as part of the transition-state mimicking scaffold, up to 56 times more potent compounds were obtained exhibiting EC(50) values down to 3 nM. Three of the inhibitors also displayed excellent activity against selected resistant isolates of HIV-1. The synthesis of 25 new and optically pure HIV-1 protease inhibitors is reported, along with methods for elongation of the inhibitor P1' side chain using microwave-accelerated, palladium-catalyzed cross-coupling reactions, the biological evaluation, and X-ray data obtained from one of the most potent analogues cocrystallized with both the wild type and the L63P, V82T, I84 V mutant of the HIV-1 protease. HIV-1 Protease Inhibitors with a Transition-State Mimic Comprising a Tertiary Alcohol: Improved Antiviral Activity in Cells.,Mahalingam AK, Axelsson L, Ekegren JK, Wannberg J, Kihlstrom J, Unge T, Wallberg H, Samuelsson B, Larhed M, Hallberg A J Med Chem. 2009 Dec 4. PMID:19961222[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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