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Title
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Inhibition of proteases with enkephalin-analogue inhibitors.
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Authors
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H.U.Demuth,
J.Silberring,
F.Nyberg.
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Ref.
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J Enzyme Inhib, 1991,
4,
289-298.
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PubMed id
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Abstract
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N-peptidyl-O-acyl hydroxylamines have proven to be effective and selective
mechanism-based inhibitors of serine and cysteine proteases as demonstrated
using enzymes with specificities for hydrophobic amino acids at the cleavage
site. Here, we report for the first time the inhibition of proteases able to
accommodate cationic amino acid side chains in their binding pockets using
compounds of this inhibitor class. Trypsin and papain are inactivated by
enkephalin-analogue diacyl hydroxylamines in a time-dependent and irreversible
manner exhibiting second-order rate constants in the range of 100-1000 M-1.s-1.
In contrast, human cerebrospinal fluid dynorphin-converting enzyme (hCSFDCE) is
inhibited only moderately by these inhibitors. Mechanistic implications have
been derived.
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