Human immunodeficiency virus protease design

Reich SH, Melnick M, Davies JF, Appelt K, Lewis KK, Fuhry MA, Pino M, Trippe AJ, Nguyen D, Dawson H, Wu B-W, Musick L, Kosa M, Kahil D, Webber S, Gehlhaar DK, Andrada D, Shetty B. Protein structure-based design of potent, orally bioavailable, nonpeptide inhibitors of human immunodeficiency virus protease. Proc. Natl. Acad. Sci. 1995 92 3298-3302. 

The human immunodeficiency virus protease (HIV-PR), an aspartic acid protease, is involved in the processing of viral polyproteins and is therefore essential for the production of new infectious virions. This enzyme is one of the best-characterized macromolecules from the vantage of drug design, with several hundred crystal structures determined to date. Protein crystallography has contributed in many... 

S. H. Reich, M. Melnick, J. F. Davies 11, K. Appelt, K. K. Lewis, M. A. Fuhry, M. Pino, A. J. Trippe, D. Nguyen, H. Dawson, B.-W. Wu, L. Musick, M. Kosa, D. Kahil, S. Webber, D. K. Gehlhaar, D. Andrada, and B. Shetty, Proc. Natl. Acad. Sci. USA, 92,3298 (1995). Protein Structure-Based Design of Potent Orally Bioavailable, Nonpeptide Inhibitors of Human Immunodeficiency Virus Protease. 

Townsend L, Devivar R, Turk S, Nassiri M, Drach J (1995) Design, synthesis, and antiviral activity of certain 2,5,6-trihalo-l-(beta-d-ribofuranosyl)benzimidazoles. J Med Chem 38 4098 105 Turlure F, Devroe E, Silver PA, Engelman A (2004) Human cell proteins and human immunodeficiency virus DNA integration. Front Biosd 9 3187-3208 Umehara T, Fukuda K, Nishikawa F, Kohara M, Hasegawa T, NisUkawa S (2005) Rational design of dual-functional aptamers that inhibit the protease and helicase activities of HCV NS3. J Biochem 137 339-347... 

DesJarlais RL, Seibel GL, Kuntz ID, Furth PS, Alvarez JC, Ortiz de Montellano PR, DeCamp DL, Babd LM, Craik CS. Structure-based design of nonpeptide inhibitors specific for the human immunodeficiency virus 1 protease. Proc Natl Acad Sci USA 1990 87 6644-8. 

Vacca, IP, Design of tight-binding human immunodeficiency virus type 1 protease inhibitors. Melhods Enzymol, 1994. 241 311-34. 

D. L. DeCamp, L. M. Babe, and C. S. Craik, Proc. Natl. Acad. Sci. U.S.A. 87, 6644 (1990). Structure-Based Design of Nonpeptide Inhibitors Specific for the Human Immunodeficiency Virus 1 Protease. 

Kaplan, A. H.(1996). Constraints on the sequence diversity of the protease of human immunodeficiency virus type 1 a guide for drug design. AIDS Res. Hum. Retroviruses 12, 849-853. 

Nelflnavir mesylate is a protease inhibitor that inhibits human immunodeficiency virus (HIV) protease, the enzyme required to form functional proteins in HIV-infected cells. It is indicated in the treatment or HIV infection in combination with other antiretroviral agents. Nelflnavir is a non-peptidic protease inhibitor that is active against both HIV-1 and HIV-2 and is formulated as the mesylate salt of a basic amine. The mean IC95 for HTV-1 in various in vitro assays is 59 nM. Like most drugs in this class, nelfinavir was a product of rational drug design. 

In the first biological application of buckyball, chemists at the University of California at San Francisco and Santa Barbara made a discovery in 1993 that could help in designing drugs to treat AIDS. The human immunodeficiency virus (HIV) that causes AIDS reproduces by synthesizing a long protein chain, which is cut into smaller segments by an enzyme called HlV-protease. One way to stop AIDS, then, might... 

Structure-Based Design of Nonpeptide Inhibitors Specific for die Human Immunodeficiency Virus 1 Protease. 

T. 1. Oprea, C. L. Waller, and G. R. Marshall, Drug Design Discovery, 12, 29 (1994). 3D-QSAR of Human Immunodeficiency Virus (I) Protease Inhibitors. III. Interpretation of CoMFA Results. 

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