Abstract
N-terminal truncation of the hexapeptide ketoacid 1 gave rise to potent tripeptide inhibitors of the hepatitis C virus NS3 protease/NS4A cofactor complex. Optimization of these tripeptides led to ketoacid 30 with an IC50 of 0.38 microM. The SAR of these tripeptides is discussed in the light of the recently published crystal structures of a ternary tripetide/NS3/NS4A complexes.
MeSH terms
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Carboxylic Acids
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Carrier Proteins / antagonists & inhibitors*
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Hepacivirus / enzymology
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Humans
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Inhibitory Concentration 50
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Intracellular Signaling Peptides and Proteins
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Models, Molecular
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Molecular Mimicry
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Oligopeptides / chemical synthesis*
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Oligopeptides / pharmacology
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Serine Proteinase Inhibitors / chemical synthesis*
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Serine Proteinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Viral Nonstructural Proteins / antagonists & inhibitors*
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Viral Proteins / antagonists & inhibitors*
Substances
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Carboxylic Acids
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Carrier Proteins
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Intracellular Signaling Peptides and Proteins
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NS3 protein, hepatitis C virus
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NS4A cofactor peptide, Hepatitis C virus
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Oligopeptides
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Serine Proteinase Inhibitors
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Viral Nonstructural Proteins
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Viral Proteins