Abstract
Proteasomal processing is conducted by three individual catalytic subunits, namely beta1, beta2, and beta5. Subunit-specific inhibitors are useful tools in dissecting the role of these individual subunits and are leads toward the development of antitumor agents. We here report that the presence of fluorinated phenylalanine derivatives in peptide based proteasome inhibitors has a profound effect on inhibitor potency and selectivity. Specifically, compound 4a emerges as one of the most beta5 specific inhibitors known to date.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Catalytic Domain / drug effects*
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Chymotrypsin / antagonists & inhibitors
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Chymotrypsin / metabolism*
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Cysteine Proteinase Inhibitors / chemical synthesis*
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Cysteine Proteinase Inhibitors / chemistry
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Cysteine Proteinase Inhibitors / pharmacology
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Inhibitory Concentration 50
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Phenylalanine / analogs & derivatives*
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Phenylalanine / chemical synthesis
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Phenylalanine / chemistry
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Phenylalanine / pharmacology
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Proteasome Endopeptidase Complex / metabolism*
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Proteasome Inhibitors
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Structure-Activity Relationship
Substances
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Cysteine Proteinase Inhibitors
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Proteasome Inhibitors
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Phenylalanine
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Chymotrypsin
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Proteasome Endopeptidase Complex