Inhibition of human endogenous retrovirus-K10 protease in cell-free and cell-based assays
| Autor: | Eric M. Towler, Chong-Hwan Chang, Robert Kuhelj, Bruce D. Korant, Christopher J. Rizzo, Prabhakar K. Jadhav |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
viruses
medicine.medical_treatment Molecular Sequence Data Endogenous retrovirus Gene Products gag Biology Biochemistry Antiviral Agents Cell-free system law.invention Substrate Specificity HIV Protease law Endopeptidases medicine Escherichia coli Tumor Cells Cultured HIV Protease Inhibitor Humans Protease Inhibitors Amino Acid Sequence Binding site Cloning Molecular Molecular Biology Sequence Deletion Protease Binding Sites integumentary system Cell-Free System Sequence Homology Amino Acid Viral Proteases Endogenous Retroviruses Teratoma Hydrogen Bonding Cell Biology HIV Protease Inhibitors In vitro Recombinant Proteins Cell culture Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization embryonic structures Recombinant DNA Sequence Alignment |
| Zdroj: | The Journal of biological chemistry. 276(20) |
| ISSN: | 0021-9258 |
| Popis: | A full-length and C-terminally truncated version of human endogenous retrovirus (HERV)-K10 protease were expressed in Escherichia coli and purified to homogeneity. Both versions of the protease efficiently processed HERV-K10 Gag polyprotein substrate. HERV-K10 Gag was also cleaved by human immunodeficiency virus, type 1 (HIV-1) protease, although at different sites. To identify compounds that could inhibit protein processing dependent on the HERV-K10 protease, a series of cyclic ureas that had previously been shown to inhibit HIV-1 protease was tested. Several symmetric bisamides acted as very potent inhibitors of both the truncated and full-length form of HERV-K10 protease, in subnanomolar or nanomolar range, respectively. One of the cyclic ureas, SD146, can inhibit the processing of in vitro translated HERV-K10 Gag polyprotein substrate by HERV-K10 protease. In addition, in virus-like particles isolated from the teratocarcinoma cell line NCCIT, there is significant accumulation of Gag and Gag-Pol precursors upon treatment with SD146, suggesting the compound efficiently blocks HERV-K Gag processing in cells. This is the first report of an inhibitor able to block cell-associated processing of Gag polypeptides of an endogenous retrovirus. |
| Databáze: | OpenAIRE |
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