Abstract
A series of dipeptide nitriles with different P3 substituents was designed to explore the S3 binding pocket of cathepsin S. Racemic 7-16 and the enantiopure derivative (R)-22 proved to be potent inhibitors of human cathepsin S and exhibited notable selectivity over human cathepsins L, K, and B. Inhibition of cathepsin F, the functional synergist of cathepsin S, was not observed. The azadipeptide analogue of 22, compound 26, was highly potent but nonselective.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cathepsin F / antagonists & inhibitors*
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Cathepsin F / metabolism*
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Cathepsins / antagonists & inhibitors*
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Cathepsins / metabolism*
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Dipeptides / chemistry
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Humans
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Inhibitory Concentration 50
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Kinetics
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Nitriles / chemical synthesis
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Nitriles / chemistry
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Nitriles / pharmacology*
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry
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Protease Inhibitors / pharmacology*
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Proteolysis / drug effects*
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Substrate Specificity
Substances
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Dipeptides
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Nitriles
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Protease Inhibitors
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Cathepsins
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cathepsin S
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Cathepsin F