TAILIEUCHUNG - Báo cáo khoa học: Halogenated benzimidazoles and benzotriazoles as inhibitors of the NTPase/helicase activities of hepatitis C and related viruses

A search has been initiated for lead inhibitors of the non-structural protein 3 (NS3)-associated NTPase/helicase activities of hepatitis C virus,the related West Nile virus, Japanese encephalitis virus and the human mitochondrial Suv3 enzyme. Random screening of a broad range of unre-lated low-molecular mass compounds,employing both RNA and DNA substrates, revealed that 4,5,6,7-tetra-bromobenzotriazole (TBBT) hitherto known as a potent highly selective inhibitor of protein kinase 2,is a good inhibitor of the helicase,but not NTPase,activity of hepa-titis C virus NTPase/helicase. . | Eur. J. Biochem. 270 1645-1653 2003 FEBS 2003 doi Halogenated benzimidazoles and benzotriazoles as inhibitors of the NTPase helicase activities of hepatitis C and related viruses Peter Borowski1 Johanna Deinert1 Sarah Schalinski1 Maria Bretner2 Krzysztof Ginalski3 4 Tadeusz Kulikowski2 and David Shugar2 4 1Abteilung fur Virologie Bernhard-Nocht-Institut fur Tropenmedizin Hamburg Germany institute of Biochemistry Biophysics Polish Academy of Sciences Warsaw Poland 3BioInfoBank Poznan Poland 4ICM University of Warsaw Poland A search has been initiated for lead inhibitors of the non-structural protein 3 NS3 -associated NTPase helicase activities of hepatitis C virus the related West Nhe virus Japanese encephalitis virus and the human mitochondrial Suv3 enzyme. Random screening of a broad range of unrelated low-molecular mass compounds employing botìi RNA and DNA substrates revealed that 4 5 6 7-tetra-bromobenzotriazole TBBT hitherto known as a potent highly selective inhibitor of protein kinase 2 is a oodd inhibitor of the helicase but not NTPase activity of hepatitis C virus NTPase helicase. The IC50 is approximately 20 M with a DNA substrate hut only 50 M with an RNA substrate. Several related analogues of TBBT were enzyme-and or substrate-specific inhibitors. For example 5di-di-chloro-1- P-D-ribofuranosyl benzotriazole DRBT was a good and seeectivei mhibitor oShhe West Nfie viuus nnzmne with an RNA substrate IC50 M but much weaker with a DNA substrate IC50 3 M . Preincubation of the enzymes but not substrates with DRBT enhanced inhibi tory potency . the IC50 vs the hepatitis C virus helicase activity was reduced from to M. No effect of preincubation was noted with TBBT lngaestmg a diSleinnt mode of interaction with the enzyme. The tetrachloro congener of TBBT 4 5 6 7 -tetrachlorobenzotriazole TCBT a much weaker inhibitor of casein kinase 2 is also a much weaker inhibitor than TBBT of all four helicases. Kinetic .

• Báo cáo khoa học
• scientific reports
• Report medicine
• traditional medicine
• immune system
• Antimicrobial
• biosynthesis
• collection of scientific reports
• industry reports philosophy of history reports
• reports in literature
• a scientific b shirt
• presentation of scientific reports
• reports on literature
• philosophy statement
• documents
• studies English language and English language communication and English language commercial
• progress reports at scientific collections
• agronomic reports
• reports in physics
• biology reports
• thematic biological
• induced geometry
• mathematical topics
• quantum mechanics
• physics
• reporting mathematics
• physics reports
• livestock reports
• physical reports
• research physicist
• specializing in physics
• mathematical statements
• mathematical equations
• English pronunciation
• presentation report
• agricultural reports
• technical crops
• bio technology
• English reports
• scientific research
• presentation reports
• mathematical knowledge
• reports of mathematics
• represented
• Wilf on packing distinct
• Tur´n density
• mathematical works
• patterns in a permutation
• statements and documents scientific reports
• reports agronomy
• biotechnology
• plants Vietnam
• specialized biological
• microbiological methods
• presenting the report
• anti bacterial properties of shrimp
• energy exchange
• engineering chicken
• Path counting
• random matrix theory
• Even circuits
• prescribed clockwise parity
• Correspondence between
• algorithmic characterizations
• Finding Induced Acyclic
• Random Digraphs
• Nonexistence results
• Hadamard like matrices
• Voltage Graphs
• Group Presentations
• Cages mathematical knowledge
• Dominance Order
• Graphical Partitions
• On the functions
• values in [α(G
• Box With Translates
• Two Given Rectangular Brick
• On the q analogue
• the sum of cubes