Abstract
The human immunodeficiency virus type-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS), codes for a virus-specific aspartic protease responsible for processing the gag and gag-pol polyproteins and for the proliferation of the retrovirus (Fig. 1). The HIV-1 protease functions as a homodimer and can recognize Phe-Pro and Tyr-Pro sequences as the cleavage site, but mammalian aspartic proteases do not have such specificity. These features provided a basis for the rational design of selective HIV protease-targeted drugs for the treatment of AIDS and related complex.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
T. Mimoto, J. Imai, S. Tanaka, N. Hattori, O. Takahashi, S. Kisanuki, Y. Nagano, M. Shintani, H. Hayashi, H. Sakikawa, K. Akaji, and Y. Kiso, Chem. Pharm. Bull., 39: 2465 (1991).
A. Wlodawer, M. Miller, M. Jaskolski, B. K. Sathyanarayana, E. Baldwin, I. T. Weber, L. M. Selk, L. Clawson, J. Schneider, and S. B. H. Kent, Science, 245: 616 (1989)
Y. Kiso, Y. Fujiwara, T. Kimura, A. Nishitani, and K. Akaji, Int. J. Peptide & Protein Res., 40: 308 (1992).
M. L. Moore, W. M. Bryan, S. A. Fakhoury, V. W. Magaard, W. F. Huffman, B. D. Dayton, T. D. Meek, L. Hyland, G. B. Dreyer, B. W. Metcalf, J. E. Strickler, J. G. Gorniak, and C. Debouck, Biochem. Biophys. Res. Commun., 159: 420 (1989).
K. Iizuka, T. Kamijo, T., H. Harada, K. Akahane, T. Kubota, H. Umeyama, T. Ishida, and Y. Kiso, J. Med. Chem., 33: 2707 (1990).
T. Mimoto, J. Imai, S. Tanaka, N. Hattori, S. Kisanuki, K. Akaji, and Y. Kiso, Chem. Pharm. Bull., 39: 3088 (1991).
N. A. Roberts, J. A. Martin, D. Kinchington, A. V. Broadhurst, J. C. Craig, I. B. Duncan, S. A. Galpin, B. K. Handa, J. Kay, A. Krohn, R. W. Lambert, J. H. Merrett, J. S. Mills, K. E. B. Parkes, S. Redshaw, A. J. Ritchie, D. L. Taylor, G. J. Thomas, and P. J. Machin, Science, 248: 358 (1990).
D. H. Rich, C. -Q. Sun, J. V. N. V. Prasad, A. Pathiasseril, M. V. Toth, G. R. Marshall, M. Clare, R. A. Mueller, and K. Houseman, J. Med. Chem., 34: 1222 (1991).
T. Mimoto, J. Imai, S. Kisanuki, S. Tanaka, N. Hattori, O. Takahashi, R. Kato, T. Yumisaki, H. Sakikawa, K. Akaji, and Y. Kiso, In: Peptide Chemistry 1991, edited by A. Suzuki, pp. 395–400. Osaka: Protein Research Foundation (1992).
T. Mimoto, J. Imai, S. Kisanuki, H. Enomoto, N. Hattori, K. Akaji, and Y. Kiso, Chem. Pharm. Bull., 40:2251 (1992).
S. Kageyama, T. Mimoto, Y. Murakawa, M. Nomizu, H. Ford, T. Shirasaka, S. Gulnik, J. Erickson, K. Takada, H. Hayashi, S. Broder, Y. Kiso, and H. Mitsuya, Antimicrob. Agents Chemother., 37: 810 (1993).
H. Mitsuya, R. Yarchoan, S. Kageyama, and S. Broder, FASEB J., 5: 2369 (1991)
S. Kageyama, J. N. Weinstein, T. Shirasaka, D. J. Kempf, D.W. Norbeck, J. J. Plattner, J. Erickson, and H. Mitsuya, Antimicrob. Agents Chemother., 36: 926 (1992).
A. Kiriyama, T. Mimoto, Y. Kiso, and K. Takada, Biopharm. Drug. Disp., 14: 199 (1993).
A. Kiriyama, T. Mimoto, S. Kisanuki, Y. Kiso, and K. Takada, Biopharm. Drug. Disp., 14: 697 (1993).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1995 Springer Science+Business Media New York
About this chapter
Cite this chapter
Kiso, Y. (1995). Design and Synthesis of HIV Protease Inhibitors Containing Allophenylnorstatine as a Transition-State Mimic. In: Takahashi, K. (eds) Aspartic Proteinases. Advances in Experimental Medicine and Biology, vol 362. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1871-6_54
Download citation
DOI: https://doi.org/10.1007/978-1-4615-1871-6_54
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5761-2
Online ISBN: 978-1-4615-1871-6
eBook Packages: Springer Book Archive