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Full-Text Articles in Social and Behavioral Sciences
A Fluorescence Quenching Assay To Discriminate Between Specific And Non-Specific Inhibitors Of Dengue Virus Protease, C Bodenreider, D Beer, T Keller, S Sonntag, D Wen, Li Yap, Y H Yau, S G Shocat, D Huang, T Zhou, A Caflisch, X C Su, Kiyoshi Ozawa, G Otting, S G. Vasudevan, J Lescar, S P. Lim
A Fluorescence Quenching Assay To Discriminate Between Specific And Non-Specific Inhibitors Of Dengue Virus Protease, C Bodenreider, D Beer, T Keller, S Sonntag, D Wen, Li Yap, Y H Yau, S G Shocat, D Huang, T Zhou, A Caflisch, X C Su, Kiyoshi Ozawa, G Otting, S G. Vasudevan, J Lescar, S P. Lim
Faculty of Science - Papers (Archive)
In drug discovery, the occurrence of false positives is a major hurdle in the search for lead compounds that can be developed into drugs. A small-molecular-weight compound that inhibits dengue virus protease at low micromolar levels was identified in a screening campaign. Binding to the enzyme was confirmed by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR). However, a structure-activity relationship study that ensued did not yield more potent leads. To further characterize the parental compound and its analogues, we developed a high-speed, low-cost, quantitative fluorescence quenching assay. We observed that specific analogues quenched dengue protease fluorescence and showed …
Discovery Of A Non-Peptidic Inhibitor Of West Nile Virus Ns3 Protease By High-Throughput Docking, Dariusz Ekonomiuk, Xun-Cheng Su, Kiyoshi Ozawa, Chrisophe Bodenreider, Siew Pheng Lim, Zheng Yin, Thomas H. Keller, David Beer, Viral Patel, Gottfried Otting, Amedeo Calflisch, Danzhi Huang
Discovery Of A Non-Peptidic Inhibitor Of West Nile Virus Ns3 Protease By High-Throughput Docking, Dariusz Ekonomiuk, Xun-Cheng Su, Kiyoshi Ozawa, Chrisophe Bodenreider, Siew Pheng Lim, Zheng Yin, Thomas H. Keller, David Beer, Viral Patel, Gottfried Otting, Amedeo Calflisch, Danzhi Huang
Faculty of Science - Papers (Archive)
No abstract provided.
Nmr Analysis Of The Dynamic Exchange Of The Ns2b Cofactor Between Open And Closed Conformations Of The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, R Qi, S G. Vasudevan, S P. Lim, G Otting
Nmr Analysis Of The Dynamic Exchange Of The Ns2b Cofactor Between Open And Closed Conformations Of The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, R Qi, S G. Vasudevan, S P. Lim, G Otting
Faculty of Science - Papers (Archive)
Background: The two-component NS2B-NS3 proteases of West Nile and dengue viruses are essential for viral replication and established targets for drug development. In all crystal structures of the proteases to date, the NS2B cofactor is located far from the substrate binding site (open conformation) in the absence of inhibitor and lining the substrate binding site (closed conformation) in the presence of an inhibitor. Methods: In this work, nuclear magnetic resonance (NMR) spectroscopy of isotope and spin-labeled samples of the West Nile virus protease was used to investigate the occurrence of equilibria between open and closed conformations in solution. Findings: In …
Nmr Study Of Complexes Between Low Molecular Mass Inhibitors And The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, Hiromasa Yagi, S P. Lim, D Wen, D Ekonomiuk, D Huang, T Keller, S Sonntag, A Caflisch, S G. Vasudevan, G Otting
Nmr Study Of Complexes Between Low Molecular Mass Inhibitors And The West Nile Virus Ns2b-Ns3 Protease, X Su, Kiyoshi Ozawa, Hiromasa Yagi, S P. Lim, D Wen, D Ekonomiuk, D Huang, T Keller, S Sonntag, A Caflisch, S G. Vasudevan, G Otting
Faculty of Science - Papers (Archive)
The two-component NS2B-NS3 protease of West Nile virus is essential for its replication and presents an attractive target for drug development. Here, we describe protocols for the high-yield expression of stable isotope-labelled samples in vivo and in vitro. We also describe the use of NMR spectroscopy to determine the binding mode of new low molecular mass inhibitors of the West Nile virus NS2B-NS3 protease which were discovered using high-throughput in vitro screening. Binding to the substrate-binding sites S1 and S3 is confirmed by intermolecular NOEs and comparison with the binding mode of a previously identified low molecular mass inhibitor. Our …