1jld
From Proteopedia
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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
