4a6c: Difference between revisions
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==Stereoselective Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Lactam Based HIV-1 Protease Inhibitors== | ==Stereoselective Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Lactam Based HIV-1 Protease Inhibitors== | ||
<StructureSection load='4a6c' size='340' side='right' caption='[[4a6c]], [[Resolution|resolution]] 1.50Å' scene=''> | <StructureSection load='4a6c' size='340' side='right'caption='[[4a6c]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4a6c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aids_virus Aids virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A6C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A6C FirstGlance]. <br> | <table><tr><td colspan='2'>[[4a6c]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Aids_virus Aids virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A6C OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A6C FirstGlance]. <br> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4a6c" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4a6c" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Immunodeficiency virus protease 3D structures|Immunodeficiency virus protease 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Aids virus]] | [[Category: Aids virus]] | ||
[[Category: HIV-1 retropepsin]] | [[Category: HIV-1 retropepsin]] | ||
[[Category: Large Structures]] | |||
[[Category: Arvela, R K]] | [[Category: Arvela, R K]] | ||
[[Category: Joshi, A A]] | [[Category: Joshi, A A]] | ||
Revision as of 16:30, 1 January 2020
Stereoselective Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Lactam Based HIV-1 Protease InhibitorsStereoselective Synthesis, X-ray Analysis, and Biological Evaluation of a New Class of Lactam Based HIV-1 Protease Inhibitors
Structural highlights
Publication Abstract from PubMedIn an effort to identify a new class of druglike HIV-1 protease inhibitors, four different stereopure beta-hydroxy gamma-lactam-containing inhibitors have been synthesized, biologically evaluated, and cocrystallized. The impact of the tether length of the central spacer (two or three carbons) was also investigated. A compound with a shorter tether and (3R,4S) absolute configuration exhibited high activity with a K(i) of 2.1 nM and an EC(50) of 0.64 muM. Further optimization by decoration of the P1' side chain furnished an even more potent HIV-1 protease inhibitor (K(i) = 0.8 nM, EC(50) = 0.04 muM). According to X-ray analysis, the new class of inhibitors did not fully succeed in forming two symmetric hydrogen bonds to the catalytic aspartates. The crystal structures of the complexes further explain the difference in potency between the shorter inhibitors (two-carbon spacer) and the longer inhibitors (three-carbon spacer). Synthesis, X-ray analysis, and biological evaluation of a new class of stereopure lactam-based HIV-1 protease inhibitors.,Wu X, Ohrngren P, Joshi AA, Trejos A, Persson M, Arvela RK, Wallberg H, Vrang L, Rosenquist A, Samuelsson BB, Unge J, Larhed M J Med Chem. 2012 Mar 22;55(6):2724-36. Epub 2012 Mar 13. PMID:22376008[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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