Interaction of Mutant Forms of the HIV-1 Protease with Substrate and Inhibitors
The protease of HIV-1 is considered to be a prime target for the treatment of AIDS with small molecular weight inhibitors. 1,2,3 Many groups have now demonstrated that compounds designed as potent inhibitors of the enzyme in vitro are effective inhibitors of viral polyprotein processing and viral spread in cultured cells.4–7 Continued effort to discover new potent inhibitors with suitable properties for use in humans is thus justified.
KeywordsSimian Immunodeficiency Virus Native Enzyme Inhibitor Binding Hydrophobic Interaction Chromatography Aspartyl Protease
Unable to display preview. Download preview PDF.
- 3.B. M. Dunn and J. Kay, Targets for antiviral chemotherapy: HlV-proteinase, Antiviral Chem. and Chemotherapy 1: 3–8 (1990).Google Scholar
- 4.T. D. Meek, D. M. Lambert, G. B. Dreyer, T. J. Carr, T. A. Tomaszek, Jr., M. L. Moore, J. E. Strickler, C. Debouck, L. J. Hyland, T. J. Matthews, B. W. Metcalf and S. R. Petteway, Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analogues, Nature 343: 90–92 (1990).PubMedCrossRefGoogle Scholar
- 5.J. Erickson, D. J. Neidhart, J. VanDrie, D. J. Kempf, X. C. Wang, D. W. Norbeck, J. J. Plattner, J. W. Rittenhouse, M. Turon, N. Wideburg, W. E. Kohlbrenner, R. Simmer, R. Helfrich, D. A. Paul and M. Knigge, Design, activity and 2.8 angstrom crystal structure of a C2 symmetric inhibitor complexed to HIV-1 protease, Science 249: 527–533 (1990).PubMedCrossRefGoogle Scholar
- 9.P. M. D. Fitzgerald, B. M. McKeever, J. P. Springer, J. C. Heimbach, C.-T. Leu, W. K. Herber, R. A. F. Dixon and P. L. Darke, Crystallographic analysis of a complex between HIV-1 protease and acetyl-pepstatin at 2.0 angstrom resolution, J. Biol. Chem. 264: 14209–14219 (1990).Google Scholar
- 10.M. Miller, J. Schneider, B. K. Sathyanarayana, M. V. Toth, G. R. Marshall, L. Clawson, L. Selk, S. B. H. Kent and A. Wlodawer, Structure of complex of synthetic HIV-1 protease with a substrate-based inhibitor at 2.3 angstrom resolution, Science 246: 1149–1152.Google Scholar
- 18.S. D. Young, P. S. Anderson, P. L. Darke, L. J. Davis, S. J. DeSolms, R. A. F. Dixon, E. A. Emini, N. Gaffin, J. P. Guare, J. R. Huff, G. Robertson, W. M. Sanders, I. S. Sigal, W. Schleif, J. P. Vacca and J. M. Wiggins, The design and synthesis of HIV protease inhibitors, Abstr. of Am. Chem. Soc. 200: 94 (1990).Google Scholar