Abstract
In this paper we report the synthesis and characterization of a novel potent and selective inhibitor of caspase-3, a member of the caspase family of cysteine proteases which plays an important role in many human disorders. This molecule represents 3(S)-acetylamino-N-[1-[(((3S)-2-hydroxy-5-oxo-tetrahydrofuran-3-yl)carbamoyl)methyl]-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]succinamic acid, a monocyclic conformationally constrained form of the tetrapeptide Ac-DEVD-H, in which a 1,4-benzodiazepine nucleus is introduced internally to the peptidic sequence.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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4-Butyrolactone / analogs & derivatives*
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4-Butyrolactone / chemical synthesis*
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4-Butyrolactone / chemistry
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4-Butyrolactone / pharmacology
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Benzodiazepinones / chemical synthesis*
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Benzodiazepinones / chemistry
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Benzodiazepinones / pharmacology
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Caspase 3
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Caspase Inhibitors*
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Caspases / chemistry
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Cell Line, Tumor
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Cell Membrane Permeability
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Humans
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Molecular Conformation
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Oligopeptides / chemistry*
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Recombinant Proteins / antagonists & inhibitors
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Recombinant Proteins / chemistry
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Stereoisomerism
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Structure-Activity Relationship
Substances
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3-acetylamino-N-(1-(((2-hydroxy-5-oxo-tetrahydrofuran-3-yl)carbamoyl)methyl)-2-oxo-5-phenyl-2,3-dihydro-1H-benzo(e)(1,4)diazepin-3-yl)succinamic acid
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Benzodiazepinones
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Caspase Inhibitors
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Oligopeptides
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Recombinant Proteins
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CASP3 protein, human
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Caspase 3
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Caspases
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4-Butyrolactone