1sbg: Difference between revisions
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|PDB= 1sbg |SIZE=350|CAPTION= <scene name='initialview01'>1sbg</scene>, resolution 2.3Å | |PDB= 1sbg |SIZE=350|CAPTION= <scene name='initialview01'>1sbg</scene>, resolution 2.3Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=IM1:(2R,4S,5S,1'S)-2-PHENYLMETHYL-4-HYDROXY-5-(TERT-BUTOXYCARBONYL)AMINO-6-PHENYL HEXANOYL-N-(1'-IMIDAZO-2-YL)-2'-METHYLPROPANAMIDE'>IM1</scene> | |LIGAND= <scene name='pdbligand=IM1:(2R,4S,5S,1'S)-2-PHENYLMETHYL-4-HYDROXY-5-(TERT-BUTOXYCARBONYL)AMINO-6-PHENYL+HEXANOYL-N-(1'-IMIDAZO-2-YL)-2'-METHYLPROPANAMIDE'>IM1</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1sbg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1sbg OCA], [http://www.ebi.ac.uk/pdbsum/1sbg PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1sbg RCSB]</span> | |||
}} | }} | ||
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[[Category: Abdel-Meguid, S.]] | [[Category: Abdel-Meguid, S.]] | ||
[[Category: Zhao, B.]] | [[Category: Zhao, B.]] | ||
[[Category: hydrolase(acid protease)]] | [[Category: hydrolase(acid protease)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:39:48 2008'' | ||
Revision as of 23:39, 30 March 2008
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| , resolution 2.3Å | |||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
AN ORALLY-BIOAVAILABLE HIV-1 PROTEASE INHIBITOR CONTAINING AN IMIDAZOLE-DERIVED PEPTIDE BOND REPLACEMENT. CRYSTALLOGRAPHIC AND PHARMACOKINETIC ANALYSIS
OverviewOverview
(2R,4S,5S,1'S)-2-Phenylmethyl-4-hydroxy-5-(tert-butoxycarbonyl) amino-6-phenylhexanoyl-N-(1'-imidazo-2-yl)-2'-methylpropanamide (compound 2) is a tripeptide analogue inhibitor of HIV-1 protease in which a C-terminal imidazole substituent constitutes an isoelectronic, structural mimic of a carboxamide group. Compound 2 is a potent inhibitor of the protease (K(i) = 18 nM) and inhibits HIV-1 acute infectivity of CD4+ T-lymphocytes (IC50 = 570 nM). Crystallographic analysis of an HIV-1 protease-compound 2 complex demonstrates that the nitrogen atoms of the imidazole ring assume the same hydrogen-bonding interactions with the protease as amide linkages in other peptide analogue inhibitors. The sole substitution of the C-terminal carboxamide of a hydroxyethylene-containing tripeptide analogue with an imidazole group imparts greatly improved pharmacokinetic and oral bioavailability properties on the compound compared to its carboxamide-containing homologue (compound 1). While the oral bioavailability of compound 1 in rats was negligible, compound 2 displayed oral bioavailabilities of 30% and 14%, respectively, in rats and monkeys.
About this StructureAbout this Structure
1SBG is a Single protein structure of sequence from Human immunodeficiency virus type 1 (isolate bh10). Full crystallographic information is available from OCA.
ReferenceReference
An orally bioavailable HIV-1 protease inhibitor containing an imidazole-derived peptide bond replacement: crystallographic and pharmacokinetic analysis., Abdel-Meguid SS, Metcalf BW, Carr TJ, Demarsh P, DesJarlais RL, Fisher S, Green DW, Ivanoff L, Lambert DM, Murthy KH, et al., Biochemistry. 1994 Oct 4;33(39):11671-7. PMID:7918383
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