1upj
From Proteopedia
(New page: 200px<br /> <applet load="1upj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1upj, resolution 2.22Å" /> '''HIV-1 PROTEASE COMP...) |
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| - | [[Image:1upj.gif|left|200px]]<br /> | + | [[Image:1upj.gif|left|200px]]<br /><applet load="1upj" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1upj, resolution 2.22Å" /> | caption="1upj, resolution 2.22Å" /> | ||
'''HIV-1 PROTEASE COMPLEX WITH U095438 [3-[1-(4-BROMOPHENYL) ISOBUTYL]-4-HYDROXYCOUMARIN'''<br /> | '''HIV-1 PROTEASE COMPLEX WITH U095438 [3-[1-(4-BROMOPHENYL) ISOBUTYL]-4-HYDROXYCOUMARIN'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1UPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with U01 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1UPJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] with <scene name='pdbligand=U01:'>U01</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UPJ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: hydrolase (acid protease)]] | [[Category: hydrolase (acid protease)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:03:35 2008'' |
Revision as of 15:03, 15 February 2008
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HIV-1 PROTEASE COMPLEX WITH U095438 [3-[1-(4-BROMOPHENYL) ISOBUTYL]-4-HYDROXYCOUMARIN
Overview
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 Structure
1UPJ is a Single protein structure of sequence from Human immunodeficiency virus 1 with as ligand. Full crystallographic information is available from OCA.
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:7658450
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