From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:3aid.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:3aid.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_3aid| PDB=3aid | SCENE= }} | | {{STRUCTURE_3aid| PDB=3aid | SCENE= }} |
| | | | |
| - | '''A NEW CLASS OF HIV-1 PROTEASE INHIBITOR: THE CRYSTALLOGRAPHIC STRUCTURE, INHIBITION AND CHEMICAL SYNTHESIS OF AN AMINIMIDE PEPTIDE ISOSTERE'''
| + | ===A NEW CLASS OF HIV-1 PROTEASE INHIBITOR: THE CRYSTALLOGRAPHIC STRUCTURE, INHIBITION AND CHEMICAL SYNTHESIS OF AN AMINIMIDE PEPTIDE ISOSTERE=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | The essential role of HIV-1 protease (HIV-1 PR) in the viral life cycle makes it an attractive target for the development of substrate-based inhibitors that may find efficacy as anti-AIDS drugs. However, resistance has arisen to potent peptidomimetic drugs necessitating the further development of novel chemical backbones for diversity based chemistry focused on probing the active site for inhibitor interactions and binding modes that evade protease resistance. AQ148 is a potent inhibitor of HIV-1 PR and represents a new class of transition state analogues incorporating an aminimide peptide isostere. A 3-D crystallographic structure of AQ148, a tetrapeptide isostere, has been determined in complex with its target HIV-1 PR to a resolution of 2.5 A and used to evaluate the specific structural determinants of AQ148 potency and to correlate structure-activity relationships within the class of related compounds. AQ148 is a competitive inhibitor of HIV-1 PR with a Ki value of 137 nM. Twenty-nine derivatives have been synthesized and chemical modifications have been made at the P1, P2, P1', and P2' sites. The atomic resolution structure of AQ148 bound to HIV-1 PR reveals both an inhibitor binding mode that closely resembles that of other peptidomimetic inhibitors and specific protein/inhibitor interactions that correlate with structure-activity relationships. The structure provides the basis for the design, synthesis and evaluation of the next generation of hydroxyethyl aminimide inhibitors. The aminimide peptide isostere is a scaffold with favorable biological properties well suited to both the combinatorial methods of peptidomimesis and the rational design of potent and specific substrate-based analogues. | + | The line below this paragraph, {{ABSTRACT_PUBMED_8894111}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8894111 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_8894111}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 30: |
Line 34: |
| | [[Category: Peptide isostere inhibitor]] | | [[Category: Peptide isostere inhibitor]] |
| | [[Category: Protease]] | | [[Category: Protease]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 20:19:06 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:35:43 2008'' |
Revision as of 02:35, 28 July 2008
Template:STRUCTURE 3aid
A NEW CLASS OF HIV-1 PROTEASE INHIBITOR: THE CRYSTALLOGRAPHIC STRUCTURE, INHIBITION AND CHEMICAL SYNTHESIS OF AN AMINIMIDE PEPTIDE ISOSTERE
Template:ABSTRACT PUBMED 8894111
About this Structure
3AID is a Single protein structure of sequence from Human immunodeficiency virus. Full crystallographic information is available from OCA.
Reference
A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere., Rutenber EE, McPhee F, Kaplan AP, Gallion SL, Hogan JC Jr, Craik CS, Stroud RM, Bioorg Med Chem. 1996 Sep;4(9):1545-58. PMID:8894111
Page seeded by OCA on Mon Jul 28 05:35:43 2008
