1upj: Difference between revisions
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[[Image:1upj.gif|left|200px]] | [[Image:1upj.gif|left|200px]] | ||
'''HIV-1 PROTEASE COMPLEX WITH U095438 [3-[1-(4-BROMOPHENYL) ISOBUTYL]-4-HYDROXYCOUMARIN''' | {{Structure | ||
|PDB= 1upj |SIZE=350|CAPTION= <scene name='initialview01'>1upj</scene>, resolution 2.22Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=U01:3-[1-(4-BROMO-PHENYL)-2-METHYL-PROPYL]-4-HYDROXY-CHROMEN-2-ONE'>U01</scene> | |||
|ACTIVITY= | |||
|GENE= | |||
}} | |||
'''HIV-1 PROTEASE COMPLEX WITH U095438 [3-[1-(4-BROMOPHENYL) ISOBUTYL]-4-HYDROXYCOUMARIN''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1UPJ is a [ | 1UPJ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UPJ OCA]. | ||
==Reference== | ==Reference== | ||
Structure-based design of novel HIV protease inhibitors: carboxamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic inhibitors., Thaisrivongs S, Watenpaugh KD, Howe WJ, Tomich PK, Dolak LA, Chong KT, Tomich CC, Tomasselli AG, Turner SR, Strohbach JW, et al., J Med Chem. 1995 Sep 1;38(18):3624-37. PMID:[http:// | Structure-based design of novel HIV protease inhibitors: carboxamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic inhibitors., Thaisrivongs S, Watenpaugh KD, Howe WJ, Tomich PK, Dolak LA, Chong KT, Tomich CC, Tomasselli AG, Turner SR, Strohbach JW, et al., J Med Chem. 1995 Sep 1;38(18):3624-37. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7658450 7658450] | ||
[[Category: Human immunodeficiency virus 1]] | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: hydrolase (acid protease)]] | [[Category: hydrolase (acid protease)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:35:09 2008'' | ||
Revision as of 15:35, 20 March 2008
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HIV-1 PROTEASE COMPLEX WITH U095438 [3-[1-(4-BROMOPHENYL) ISOBUTYL]-4-HYDROXYCOUMARIN
OverviewOverview
The low oral bioavailability and rapid biliary excretion of peptide-derived HIV protease inhibitors have limited their utility as potential therapeutic agents. Our broad screening program to discover nonpeptidic HIV protease inhibitors had previously identified compound II (phenprocoumon, K(i) = 1 muM) as a lead template. Crystal structures of HIV protease complexes containing the peptide-derived inhibitor I (1-(naphthoxyacetyl)-L-histidyl-5(S)-amino-6-cyclohexyl-3 (R),4(R)-dihydroxy-2(R)-isopropylhexanoyl-L-isoleucine N-(2-pyridylmethyl)amide) and nonpeptidic inhibitors, such as phenprocoumon (compound II), provided a rational basis for the structure-based design of more active analogues. This investigation reports on the important finding of a carboxamide functionally appropriately added to the 4-hydroxycoumarin and the 4-hydroxy-2-pyrone templates which resulted in a new promising series of nonpeptidic HIV protease inhibitors with improved enzyme-binding affinity. The most active diastereomer of the carboxamide-containing compound XXIV inhibited HIV-1 protease with a K(i) value of 0.0014 muM. This research provides a new design direction for the discovery of more potent HIV protease inhibitors as potential therapeutic agents for the treatment of HIV infection.
About this StructureAbout this Structure
1UPJ is a Single protein structure of sequence from Human immunodeficiency virus 1. Full crystallographic information is available from OCA.
ReferenceReference
Structure-based design of novel HIV protease inhibitors: carboxamide-containing 4-hydroxycoumarins and 4-hydroxy-2-pyrones as potent nonpeptidic inhibitors., Thaisrivongs S, Watenpaugh KD, Howe WJ, Tomich PK, Dolak LA, Chong KT, Tomich CC, Tomasselli AG, Turner SR, Strohbach JW, et al., J Med Chem. 1995 Sep 1;38(18):3624-37. PMID:7658450
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