HIV protease-ligand complexesCurrent Opinion in Structural Biology 1993, 3: 868874

Abstract HIV-1 protease remains a promising target for the treatment of AIDS, and research continues in many laboratories to exploit a knowledge of the structure of the protease and its interactions with inhibitors in the development of an AIDS therapy. Structures of HIV-1 protease in complex with peptide-based inhibitors continue to be reported, and recently structures have appeared for a number of compounds that are not fundamentally peptidyl in nature, compounds that were identified as inhibitors either by screening methods or by structure-based database searches. Three structures of the closely related HIV-2 protease in complex with peptide-based inhibitors have now also been determined.

[1]  Narmada Thanki,et al.  Crystal structure of a complex of HIV‐1 protease with a dihydroxyethylene‐containing inhibitor: Comparisons with molecular modeling , 1992, Protein science : a publication of the Protein Society.

[2]  M. Weir,et al.  Penicillin derived C2-symmetric dimers as novel inhibitors of HIV-1 proteinase. , 1992, Journal of medicinal chemistry.

[3]  A. Tomasselli,et al.  The crystallographic structure of the protease from human immunodeficiency virus type 2 with two synthetic peptidic transition state analog inhibitors. , 1993, The Journal of biological chemistry.

[4]  T L Blundell,et al.  The 3-D structure of HIV-1 proteinase and the design of antiviral agents for the treatment of AIDS. , 1990, Trends in biochemical sciences.

[5]  A. Berger,et al.  On the size of the active site in proteases. I. Papain. , 1967, Biochemical and biophysical research communications.

[6]  K. Murthy,et al.  The crystal structures at 2.2-A resolution of hydroxyethylene-based inhibitors bound to human immunodeficiency virus type 1 protease show that the inhibitors are present in two distinct orientations. , 1994 .

[7]  M. Hatada,et al.  Novel binding mode of highly potent HIV-proteinase inhibitors incorporating the (R)-hydroxyethylamine isostere. , 1991, Journal of medicinal chemistry.

[8]  J. Huff,et al.  HIV protease: a novel chemotherapeutic target for AIDS. , 1991, Journal of medicinal chemistry.

[9]  J. Springer,et al.  Binding of a Reduced-Peptide Inhibitor and a Statine-Containing Inhibitor to the Protease from the Human Immunodeficiency Virus , 1991 .

[10]  M. Katharine Holloway,et al.  X-Ray Crystal Structure of the HIV Protease Complex with L-700,417, an Inhibitor with Pseudo C2 Symmetry , 1991 .

[11]  A M Hassell,et al.  A symmetric inhibitor binds HIV-1 protease asymmetrically. , 1993, Biochemistry.

[12]  M. Jaskólski,et al.  Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease. , 1989, Science.

[13]  A Wlodawer,et al.  Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 A resolution. , 1989, Science.

[14]  D. Norbeck,et al.  Design, activity, and 2.8 A crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease. , 1990, Science.

[15]  M. Navia,et al.  Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1 , 1989, Nature.

[16]  J M Blaney,et al.  A geometric approach to macromolecule-ligand interactions. , 1982, Journal of molecular biology.

[17]  C. Craik,et al.  Regulation of autoproteolysis of the HIV-1 and HIV-2 proteases with engineered amino acid substitutions. , 1993, The Journal of biological chemistry.

[18]  R. DesJarlais,et al.  Inhibition of human immunodeficiency virus-1 protease by a C2-symmetric phosphinate. Synthesis and crystallographic analysis. , 1993, Biochemistry.

[19]  John P. Overington,et al.  X-ray analysis of HIV-1 proteinase at 2.7 Å resolution confirms structural homology among retroviral enzymes , 1989, Nature.

[20]  P Murray-Rust,et al.  A series of penicillin-derived C2-symmetric inhibitors of HIV-1 proteinase: structural and modeling studies. , 1993, Journal of medicinal chemistry.

[21]  I. Kuntz,et al.  Structure-based design of nonpeptide inhibitors specific for the human immunodeficiency virus 1 protease. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[22]  C. Debouck,et al.  The HIV-1 protease as a therapeutic target for AIDS. , 1992, AIDS research and human retroviruses.

[23]  A Wlodawer,et al.  X-ray crystallographic structure of a complex between a synthetic protease of human immunodeficiency virus 1 and a substrate-based hydroxyethylamine inhibitor. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[24]  A. Wlodawer,et al.  The complexities of AIDS : an assessment of the HIV protease as a therapeutic target , 1991 .

[25]  L J Davis,et al.  Active human immunodeficiency virus protease is required for viral infectivity. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C M Cook,et al.  The three-dimensional x-ray crystal structure of HIV-1 protease complexed with a hydroxyethylene inhibitor. , 1991, Advances in experimental medicine and biology.

[27]  Mark A. Murcko,et al.  Use of structural information in drug design , 1992, Current Biology.

[28]  A. Wlodawer,et al.  Structure-based inhibitors of HIV-1 protease. , 1993, Annual review of biochemistry.

[29]  R. Poljak,et al.  The three-dimensional structure of the aspartyl protease from the HIV-1 isolate BRU. , 1991, Biochimie.

[30]  A M Hassell,et al.  Hydroxyethylene isostere inhibitors of human immunodeficiency virus-1 protease: structure-activity analysis using enzyme kinetics, X-ray crystallography, and infected T-cell assays. , 1992, Biochemistry.

[31]  R. Dixon,et al.  Crystallographic analysis of a complex between human immunodeficiency virus type 1 protease and acetyl-pepstatin at 2.0-A resolution. , 1991, The Journal of biological chemistry.

[32]  P. Darke,et al.  Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1' phenyl substituents: X-ray crystal structure assisted design. , 1992, Journal of Medicinal Chemistry.

[33]  D. Norbeck,et al.  Chapter 15. HIV Protease Inhibitors , 1991 .

[34]  J. A. Martin,et al.  Recent advances in the design of HIV proteinase inhibitors. , 1992, Antiviral research.

[35]  Comparison of Crystal Structures of Inhibitor Complexes of the Human Immunodeficiency Virus Protease , 1992 .

[36]  J. Springer,et al.  Structure and function of retroviral proteases. , 1991, Annual review of biophysics and biophysical chemistry.

[37]  A Wlodawer,et al.  Structure at 2.5-A resolution of chemically synthesized human immunodeficiency virus type 1 protease complexed with a hydroxyethylene-based inhibitor. , 1991, Biochemistry.