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| [[Image:2hb3.gif|left|200px]] | | {{Seed}} |
| | [[Image:2hb3.png|left|200px]] |
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| {{STRUCTURE_2hb3| PDB=2hb3 | SCENE= }} | | {{STRUCTURE_2hb3| PDB=2hb3 | SCENE= }} |
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| '''Wild-type HIV-1 Protease in complex with potent inhibitor GRL06579'''
| | ===Wild-type HIV-1 Protease in complex with potent inhibitor GRL06579=== |
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| ==Overview==
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| Structure-based design and synthesis of novel HIV protease inhibitors are described. The inhibitors are designed specifically to interact with the backbone of HIV protease active site to combat drug resistance. Inhibitor 3 has exhibited exceedingly potent enzyme inhibitory and antiviral potency. Furthermore, this inhibitor maintains impressive potency against a wide spectrum of HIV including a variety of multi-PI-resistant clinical strains. The inhibitors incorporated a stereochemically defined 5-hexahydrocyclopenta[b]furanyl urethane as the P2-ligand into the (R)-(hydroxyethylamino)sulfonamide isostere. Optically active (3aS,5R,6aR)-5-hydroxy-hexahydrocyclopenta[b]furan was prepared by an enzymatic asymmetrization of meso-diacetate with acetyl cholinesterase, radical cyclization, and Lewis acid-catalyzed anomeric reduction as the key steps. A protein-ligand X-ray crystal structure of inhibitor 3-bound HIV-1 protease (1.35 A resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16913714}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16913714 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16913714}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Weber, I T.]] | | [[Category: Weber, I T.]] |
| [[Category: Active-site cavity protease inhibitor catalytic aspartic acid]] | | [[Category: Active-site cavity protease inhibitor catalytic aspartic acid]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:04:45 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 17:20:28 2008'' |
