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| [[Image:2upj.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_2upj| PDB=2upj | SCENE= }} | | {{STRUCTURE_2upj| PDB=2upj | SCENE= }} |
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| '''HIV-1 PROTEASE COMPLEX WITH U100313 ([3-[[3-[CYCLOPROPYL [4-HYDROXY-2OXO-6-[1-(PHENYLMETHYL)PROPYL]-2H-PYRAN-3-YL] METHYL]PHENYL]AMINO]-3-OXO-PROPYL]CARBAMIC ACID TERT-BUTYL ESTER)'''
| | ===HIV-1 PROTEASE COMPLEX WITH U100313 ([3-[[3-[CYCLOPROPYL [4-HYDROXY-2OXO-6-[1-(PHENYLMETHYL)PROPYL]-2H-PYRAN-3-YL] METHYL]PHENYL]AMINO]-3-OXO-PROPYL]CARBAMIC ACID TERT-BUTYL ESTER)=== |
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| ==Overview==
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| 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. | | The line below this paragraph, {{ABSTRACT_PUBMED_7658450}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 7658450 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_7658450}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Mulichak, A M.]] | | [[Category: Mulichak, A M.]] |
| [[Category: Watenpaugh, K D.]] | | [[Category: Watenpaugh, K D.]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 17:28:47 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 06:48:14 2008'' |
