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''' | ==Macrocyclic Transition-State Mimicking HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol== | ||
<StructureSection load='4cps' size='340' side='right' caption='[[4cps]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4cps]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CPS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CPS FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1T8:METHYL+[(2S)-1-(2-{3-[(3R,6S,10Z)-3-HYDROXY-4,7-DIOXO-6-(PROPAN-2-YL)-5,8-DIAZABICYCLO[11.2.2]HEPTADECA-1(15),10,13,16-TETRAEN-3-YL]PROPYL}-2-[4-(PYRIDIN-3-YL)BENZYL]HYDRAZINYL)-3,3-DIMETHYL-1-OXOBUTAN-2-YL]CARBAMATE'>1T8</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cpq|4cpq]], [[4cpr|4cpr]], [[4cpt|4cpt]], [[4cpu|4cpu]], [[4cpw|4cpw]], [[4cpx|4cpx]]</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=4cps FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cps OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4cps RCSB], [http://www.ebi.ac.uk/pdbsum/4cps PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Seven novel tertiary alcohol containing linear HIV-1 protease inhibitors (PIs), decorated at the para position of the benzyl group in the P1' side with (hetero)aromatic moieties, were synthesized and biologically evaluated. To study the inhibition and antiviral activity effect of P1-P3 macrocyclization, 14- and 15-membered macrocyclic PIs were prepared by ring-closing metathesis of the corresponding linear PIs. The macrocycles were more active than the linear precursors and compound 10f, with a 2-thiazolyl group in the P1' position, was the most potent PI of this new series (Ki 2.2 nM, EC50 0.2 muM). Co-crystallized complexes of both linear and macrocyclic PIs with the HIV-1 protease enzyme were prepared and analyzed. | |||
Synthesis of P1'-functionalized macrocyclic transition-state mimicking HIV-1 protease inhibitors encompassing a tertiary alcohol.,De Rosa M, Unge J, Motwani HV, Rosenquist A, Vrang L, Wallberg H, Larhed M J Med Chem. 2014 Aug 14;57(15):6444-57. doi: 10.1021/jm500434q. Epub 2014 Aug 1. PMID:25054811<ref>PMID:25054811</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: HIV-1 retropepsin]] | |||
[[Category: DeRosa, M]] | |||
[[Category: Larhed, M]] | |||
[[Category: Motwani, H V]] | |||
[[Category: Rosenquist, A]] | |||
[[Category: Unge, J]] | |||
[[Category: Vrang, L]] | |||
[[Category: Wallberg, H]] | |||
[[Category: Hydrolase]] | |||
[[Category: Inhibitor]] | |||
[[Category: Rational drug design]] | |||
Revision as of 15:44, 17 December 2014
Macrocyclic Transition-State Mimicking HIV-1 Protease Inhibitors Encompassing a Tertiary AlcoholMacrocyclic Transition-State Mimicking HIV-1 Protease Inhibitors Encompassing a Tertiary Alcohol
Structural highlights
Publication Abstract from PubMedSeven novel tertiary alcohol containing linear HIV-1 protease inhibitors (PIs), decorated at the para position of the benzyl group in the P1' side with (hetero)aromatic moieties, were synthesized and biologically evaluated. To study the inhibition and antiviral activity effect of P1-P3 macrocyclization, 14- and 15-membered macrocyclic PIs were prepared by ring-closing metathesis of the corresponding linear PIs. The macrocycles were more active than the linear precursors and compound 10f, with a 2-thiazolyl group in the P1' position, was the most potent PI of this new series (Ki 2.2 nM, EC50 0.2 muM). Co-crystallized complexes of both linear and macrocyclic PIs with the HIV-1 protease enzyme were prepared and analyzed. Synthesis of P1'-functionalized macrocyclic transition-state mimicking HIV-1 protease inhibitors encompassing a tertiary alcohol.,De Rosa M, Unge J, Motwani HV, Rosenquist A, Vrang L, Wallberg H, Larhed M J Med Chem. 2014 Aug 14;57(15):6444-57. doi: 10.1021/jm500434q. Epub 2014 Aug 1. PMID:25054811[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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