HIV-proteinase

Hansson, T., Aqvist, J. Estimation of binding free energies for HIV proteinase inhibitors by molecular dynamics simulations. Prot. Eng. 8 (1995) 1137-1144... 

Hansson T and J Aqvist 1995. Estimation of Binding Free Energies for HIV Proteinase Inhibitors b Molecular Dynamics Simulations. Protein Engineering 8 1137-1144. 

Craig JC, Duncan IB, Hockley D, Grief C, Roberts NA, Mills JS (1991) Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) proteinase. Antiviral Res 16 295-305... 

T. Hansson and J. Aqvist, Estimation of binding free energies for HIV proteinase... 

Roberts NA, Martin JA, Kinchington D, Broadhurst AV, Craig JC, Duncan IB, Galpin SA, Handa BJ, Kay J, Krohn A, Lambert RW, Merrett JH, Mills JS, Parkes KEB, Redshaw S, Ritchie AJ, Taylor DL, Thomas GJ, Machin PJ. Rational design of peptide-based HIV proteinase inhibitors. 1990 248 358-361. 

Craig JC, Duncan IB, Whittaker L, Roberts NA. Antiviral synergy between inhibitors of HIV proteinase and reverse transcriptase. Antiviral Chem Chemother 1993 4 161-166. 

Krohn A, Redshaw S, Ritchie JC, Graves BJ, Hatada MH. Novel binding mode of highly potent HIV proteinase inhibitors incorporating the (R)-hydroxyethylamine isostere. J. Med. Chem. 1991 34 3340-3342. 

Ettmayer, P. Billich, A. Hecht, P. Rosen-wirth, B. Gstach, H. Paracyclophanes a 357 novel dass of water-soluble inhibitors of HIV proteinase./. Med. Chem. 1996, 39, 3291—3299. 

Williams PEO, Muirhead GJ, Madigan MJ, et al. Disposition and bioavailability of the HIV-proteinase inhibitor, Ro 31-8959, after single doses in healthy volunteers. Br J Clin Pharmacol 1992 34 155P-156P. 

Fig. 2. Fluorescence micrographs of C. albicans SC5314 adhering on epithelial Vero cells in the absence a and in the presence b of the HIV proteinase inhibitor ritonavir at a concentration of 200 (rm. 

HIV proteinase inhibitors may display a specific anti-Sap activity leading to a reduced number of C. albicans yeasts on epithelial cells. Therefore, development of specific aspartic proteinase inhibitors might be useful in the treatment of mucosal candidiasis. The precise function of Candida Saps in the adherence process is not known, but two hypotheses can be advanced (1) the Candida Saps could act as ligands to surface proteins of the specific host cells, which do... 

Korting HC, Schaller M, Eder G, Hamm G, Bohmer U, Hube B Effects of the human immunodeficiency vims (HIV) proteinase inhibitors Saquinavir and Indinavir on in vitro activities of secreted aspartyl proteinases of Candida albicans isolates from HIV-infected patients. Antimicrob Agents Chemother 1999 43 2038-2042. 

Roberts, N. A., et al. (1990) Rational design of peptide based HIV proteinase inhibitors. Science 248, 358-361. 

The structure of the carrot CE 8 pectin methyl esterase was very similar to the bacterial enzyme, although for reasons which are not clear a mechanism involving one of the aspartates as a nucleophile, rather than a general base, was preferred to the aspartate protease mechanism. Such mechanisms have been previously proposed for the aspartic proteinases, but were thoroughly disproved when one of this class of enzymes, the HIV proteinase, was found to... 

Fig. 26.20 Structure-based design of nonpeptide inhibitors of the HIV proteinase. For explanation, see (Adapted, with permission, from Lam, P.Y.S.et al. (1994) Science 263 380-384. Copyright 1994 by the AAAS.)...

Fig. 27.4 Structures of the aspartic proteinases superfamily (a) HIV proteinases (b) rennin.

In 1985 Toh et recognized a sequence in the Rous sarcoma virus (RSV) genome that resembled that of the Asp-Thr-Gly motif of aspartic proteinases, and a similar sequence was subsequently identified in HIV. This led to the suggestion that retroviruses contained a dimer which resembled the putative dimeric ancestor of the pepsin-like aspartic proteinases.The analogy, supported by observations that an HTV proteinase was sensistive to pepstatin, led to interest in the development of HIV proteinase inhibitors. It was later noted that HIV requires a specific protease for the maturation of its components and therefore inhibition of this protease could represent a therapeutic approach to the treatment of AIDs. 

Novel binding mode of highly potent HIV-proteinase inhibitors incorporating... 

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