The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
A Synthetic HIV-1 Protease Inhibitor with Antiviral Activity Arrests HIV-Like Particle Maturation
Abstract
A synthetic peptidemimetic substrate of the human immunodeficiency virus 1 (HIV-1) protease with a nonhydrolyzable pseudodipeptidyl insert at the protease cleavage site was prepared. The peptide U-81749 inhibited recombinant HIV-1 protease in vitro (inhibition constant K i of 70 nanomolar) and HIV-1 replication in human peripheral blood lymphocytes (inhibitory concentration IC 50 of 0.1 to 1 micromolar). Moreover, 10 micromolar concentrations of U-81749 significantly inhibited proteolysis of the HIV-1 gag polyprotein (p55) to the mature viral structural proteins p24 and p17 in cells infected with a recombinant vaccinia virus expressing the HIV-1 gag-pol genes. The HIV-1 like particles released from inhibitor-treated cells contained almost exclusively p55 and other gag precursors, but not p24. Incubation of HIV-like particles recovered from drug-treated cultures in drug-free medium indicated that inhibition of p55 proteolysis was at least partially reversible, suggesting that U-81749 was present within the particles.
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Citations
Cites
The Efficacy of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related Complex
Fischl, M. A., Richman, D. D., Grieco, M. H., Gottlieb, M. S., Volberding, P. A., Laskin, O. L., Leedom, J. M., Groopman, J. E., Mildvan, D., Schooley, R. T., et al. (1987) · New England Journal of Medicine · doi:10.1056/nejm198707233170401 · Cited by 2,995
The Toxicity of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related Complex
Richman, D. D., Fischl, M. A., Grieco, M. H., Gottlieb, M. S., Volberding, P. A., Laskin, O. L., Leedom, J. M., Groopman, J. E., Mildvan, D., Hirsch, M. S., et al. (1987) · New England Journal of Medicine · doi:10.1056/nejm198707233170402 · Cited by 1,199
Characterization of ribosomal frameshifting in HIV-1 gag-pol expression
Jacks, T., Power, M. D., Masiarz, F. R., Luciw, P. A., Barr, P. J., & Varmus, H. E. (1988) · Nature · doi:10.1038/331280a0 · Cited by 966
Cited by
INHIBITORS OF HIV-1 PROTEASE: A Major Success of Structure-Assisted Drug Design
Wlodawer, A., & Vondrasek, J. (1998) · Annual Review of Biophysics and Biomolecular Structure · doi:10.1146/annurev.biophys.27.1.249 · Cited by 734
Huang, M., Orenstein, J. M., Martin, M. A., & Freed, E. O. (1995) · Journal of Virology · doi:10.1128/jvi.69.11.6810-6818.1995 · Cited by 486
Jaskolski, M., Tomasselli, A. G., Sawyer, T. K., Staples, D. G., Heinrikson, R. L., Schneider, J., Kent, S. B. H., & Wlodawer, A. (1991) · Biochemistry · doi:10.1021/bi00220a023 · Cited by 227
Self-citationAkhtar, A., Hussain, W., & Rasool, N. (2019) · Universitas Scientiarum · doi:10.11144/javeriana.sc24-3.artf · Cited by 27
Metadata
- Authors
- McQuade, T. J., Tomasselli, A. G., Liu, L., Karacostas, V., Moss, B., Sawyer, T. K., Heinrikson, R. L., & Tarpley, W. G.
- Venue
- Science
- Published
- 1990-01-26
- Volume
- 247
- Issue
- 4941
- Pages
- 454-456
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2080786231
- Cited by
- 374
- References
- 3
- FWCI
- 48.43
- Type
- journal article
- Language
- en
- Open access
- closed
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