A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease

A designed P1 cysteine mimetic for covalent and non-covalent inhibitors of HCV NS3 protease

The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K(i) 30 nM) and reversible covalent inhibi...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2002-02, Vol.12 (4), p.701
Hauptverfasser: Narjes, Frank, Koehler, Konrad F, Koch, Uwe, Gerlach, Benjamin, Colarusso, Stefania, Steinkühler, Christian, Brunetti, Mirko, Altamura, Sergio, De Francesco, Raffaele, Matassa, Victor G
Format: Artikel
Sprache:eng
Schlagworte:
Cysteine
Drug Design
Hepacivirus - enzymology
Humans
Models, Molecular
Molecular Mimicry
Oligopeptides - chemical synthesis
Oligopeptides - pharmacology
Structure-Activity Relationship
Viral Nonstructural Proteins - antagonists & inhibitors
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Zusammenfassung:The difluoromethyl group was designed by computational chemistry methods as a mimetic of the canonical P1 cysteine thiol for inhibitors of the hepatitis C virus NS3 protease. This modification led to the development of competitive, non-covalent inhibitor 4 (K(i) 30 nM) and reversible covalent inhibitors (6, K(i) 0.5 nM; and 8 K*(i) 10 pM).
ISSN:0960-894X
DOI:10.1016/S0960-894X(01)00842-3