| Autor: |
D L, Flynn, D P, Becker, V M, Dilworth, M K, Highkin, P J, Hippenmeyer, K A, Houseman, L M, Levine, M, Li, A E, Moormann, A, Rankin, M V, Toth, C I, Villamil, A J, Wittwer, B C, Holwerda |
| Rok vydání: |
1997 |
| Předmět: |
|
| Zdroj: |
Drug design and discovery. 15(1) |
| ISSN: |
1055-9612 |
| Popis: |
The herpesvirus protease is a recently identified enzyme which is essential for viral replication. It is found in all herpesviruses and offers a new molecular target for therapeutic intervention. Its genomic structure has recently been described and consists of a large open reading frame which encodes a fusion protein containing an amino-terminal protease domain in-frame with a carboxyl-terminal "assembly protein-like" domain. Auto-processing releases the amino-terminal protease as a maturational enzyme. The herpesvirus protease has been characterized as a novel serine protease. Four surface accessible sulfhydryl groups have been identified in the human cytomegalovirus (HCMV) protease. Utilizing a fluorogenic DABCYL-EDANS substrate assay, directed screening has identified a class of sulfhydryl-modifying benzimidazolylmethyl sulfoxides which inhibits recombinant HCMV protease. Site-directed mutagenesis studies suggest oxidative modification of surface-accessible HCMV protease Cys138 (and possibly Cys161) by this class of inhibitors. The benzimidazolylmethyl sulfoxide 1 inhibits HCMV protease (IC50 = 1.9 microM), exhibits selectivity vs. mammalian serine proteases, and exhibits antiviral activity in an HCMV infected cell culture assay. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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