Rational Design of Peptide-Based HIV Proteinase Inhibitors
- 20 April 1990
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 248 (4953) , 358-361
- https://doi.org/10.1126/science.2183354
Abstract
A series of peptide derivatives based on the transition-state mimetic concept has been designed that inhibit the proteinase from the human immunodeficiency virus (HIV). The more active compounds inhibit both HIV-1 and HIV-2 proteinases in the nanomolar range with little effect at 10 micromolar against the structurally related human aspartic proteinases. Proteolytic cleavage of the HIV-1 gag polyprotein (p55) to the viral structural protein p24 was inhibited in chronically infected CEM cells. Antiviral activity was observed in the nanomolar range (with one compound active below 10 nanomolar) in three different cell systems, as assessed by p24 antigen and syncytium formation. Cytotoxicity was not detected at 10 and 5 micromolar in C8166 and JM cells, respectively, indicating a high therapeutic index for this new class of HIV proteinase inhibitors.This publication has 22 references indexed in Scilit:
- A Synthetic HIV-1 Protease Inhibitor with Antiviral Activity Arrests HIV-Like Particle MaturationScience, 1990
- Inhibition of HIV-1 protease in infected T-lymphocytes by synthetic peptide analoguesNature, 1990
- Inhibition of the aspartic proteinase from HIV‐2FEBS Letters, 1989
- Renin inhibitors. Synthesis of transition-state analog inhibitors containing phosphorus acid derivatives at the scissile bondJournal of Medicinal Chemistry, 1989
- Effective blocking of HIV‐1 proteinase activity by characteristic inhibitors of aspartic proteinasesFEBS Letters, 1989
- Peptide substrates and inhibitors of the HIV-1 proteaseBiochemical and Biophysical Research Communications, 1989
- Human renin: A new class of inhibitorsBiochemical and Biophysical Research Communications, 1986
- Complete nucleotide sequence of the AIDS virus, HTLV-IIINature, 1985
- Potent new inhibitors of human reninNature, 1982
- Characterization of EBV‐genome negative “null” and “T” cell lines derived from children with acute lymphoblastic leukemia and leukemic transformed non‐Hodgkin lymphomaInternational Journal of Cancer, 1977