1jld
From Proteopedia
(New page: 200px<br /> <applet load="1jld" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jld, resolution 2.5Å" /> '''POTENT HIV PROTEASE ...) |
|||
| Line 1: | Line 1: | ||
| - | [[Image:1jld.gif|left|200px]]<br /> | + | [[Image:1jld.gif|left|200px]]<br /><applet load="1jld" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1jld" size=" | + | |
caption="1jld, resolution 2.5Å" /> | caption="1jld, resolution 2.5Å" /> | ||
'''POTENT HIV PROTEASE INHIBITORS CONTAINING A NOVEL (HYDROXYETHYL)AMIDE ISOSTERE'''<br /> | '''POTENT HIV PROTEASE INHIBITORS CONTAINING A NOVEL (HYDROXYETHYL)AMIDE ISOSTERE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A series of HIV protease inhibitors containing a novel | + | A series of HIV protease inhibitors containing a novel (hydroxyethyl)amidosuccinoyl core has been synthesized. These peptidomimetic structures inhibit viral protease activity at low nanomolar concentrations (IC50 < 10 nM for HIV-1 protease). The inhibition constant (Ki) for inhibitor 19 was determined to be 7.5 pM against HIV-1 and 1.2 nM against HIV-2 proteases, respectively. Several compounds (19-24) inhibited HIV-1 replication in cell culture assays with 50% effective concentrations (EC50) = 3.7-35 nM. This series of inhibitors was found to exhibit poor bioavailability (< 10%) in the rat, following oral administration. The synthesis and biological properties of these compounds are discussed. In addition, an X-ray structure of one of these inhibitors (23) in complex with HIV-2 protease provides insight into the binding mode of this novel class of HIV protease inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 1JLD 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 QNC as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http:// | + | 1JLD 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=QNC:'>QNC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/HIV-1_retropepsin HIV-1 retropepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.16 3.4.23.16] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JLD OCA]. |
==Reference== | ==Reference== | ||
| Line 21: | Line 20: | ||
[[Category: polyprotein]] | [[Category: polyprotein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:24:02 2008'' |
Revision as of 11:24, 21 February 2008
|
POTENT HIV PROTEASE INHIBITORS CONTAINING A NOVEL (HYDROXYETHYL)AMIDE ISOSTERE
Overview
A series of HIV protease inhibitors containing a novel (hydroxyethyl)amidosuccinoyl core has been synthesized. These peptidomimetic structures inhibit viral protease activity at low nanomolar concentrations (IC50 < 10 nM for HIV-1 protease). The inhibition constant (Ki) for inhibitor 19 was determined to be 7.5 pM against HIV-1 and 1.2 nM against HIV-2 proteases, respectively. Several compounds (19-24) inhibited HIV-1 replication in cell culture assays with 50% effective concentrations (EC50) = 3.7-35 nM. This series of inhibitors was found to exhibit poor bioavailability (< 10%) in the rat, following oral administration. The synthesis and biological properties of these compounds are discussed. In addition, an X-ray structure of one of these inhibitors (23) in complex with HIV-2 protease provides insight into the binding mode of this novel class of HIV protease inhibitors.
About this Structure
1JLD is a Single protein structure of sequence from Human immunodeficiency virus 1 with as ligand. Active as HIV-1 retropepsin, with EC number 3.4.23.16 Full crystallographic information is available from OCA.
Reference
Potent HIV protease inhibitors containing a novel (hydroxyethyl)amide isostere., Beaulieu PL, Wernic D, Abraham A, Anderson PC, Bogri T, Bousquet Y, Croteau G, Guse I, Lamarre D, Liard F, Paris W, Thibeault D, Pav S, Tong L, J Med Chem. 1997 Jul 4;40(14):2164-76. PMID:9216835
Page seeded by OCA on Thu Feb 21 13:24:02 2008
