Peptide-boronic acid inhibitors of flaviviral proteases: medicinal chemistry and structural biology
A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Stru...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 12, 2017
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| In: |
Journal of medicinal chemistry
Year: 2017, Volume: 60, Issue: 1, Pages: 511-516 |
| ISSN: | 1520-4804 |
| DOI: | 10.1021/acs.jmedchem.6b01021 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1021/acs.jmedchem.6b01021
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| Author Notes: | Christoph Nitsche, Linlin Zhang, Lena F. Weigel, Jonas Schilz, Dominik Graf, Ralf Bartenschlager, Rolf Hilgenfeld, and Christian D. Klein |
| Summary: | A thousand-fold affinity gain is achieved by introduction of a C-terminal boronic acid moiety into dipeptidic inhibitors of the Zika, West Nile, and dengue virus proteases. The resulting compounds have Ki values in the two-digit nanomolar range, are not cytotoxic, and inhibit virus replication. Structure-activity relationships and a high resolution X-ray cocrystal structure with West Nile virus protease provide a basis for the design of optimized covalent-reversible inhibitors aimed at emerging flaviviral pathogens. |
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| Item Description: | Online erschienen: November 28, 2016 Gesehen am 08.05.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1520-4804 |
| DOI: | 10.1021/acs.jmedchem.6b01021 |