Abstract
Substrate-based tetrapeptide inhibitors with various warheads were designed, synthesized, and evaluated against the Dengue virus NS3 protease. Effective inhibition was achieved by peptide inhibitors with electrophilic warheads such as aldehyde, trifluoromethyl ketone, and boronic acid. A boronic acid has the highest affinity, exhibiting a K(i) of 43 nM.
MeSH terms
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Boronic Acids / chemistry
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Chemistry, Pharmaceutical / methods*
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Dengue Virus / enzymology*
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Dose-Response Relationship, Drug
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Drug Design*
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Enzyme Inhibitors / pharmacology
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Ketones / chemistry
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Kinetics
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Models, Chemical
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Peptides / chemistry
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Peptides / pharmacology*
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Protease Inhibitors / chemistry*
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Protease Inhibitors / pharmacology
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RNA Helicases / antagonists & inhibitors
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RNA Helicases / chemistry
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Serine Endopeptidases / chemistry
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Substrate Specificity
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Time Factors
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Nonstructural Proteins / chemistry*
Substances
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Boronic Acids
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Enzyme Inhibitors
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Ketones
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NS3 protein, flavivirus
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Peptides
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Protease Inhibitors
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Viral Nonstructural Proteins
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Serine Endopeptidases
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RNA Helicases