Abstract
Optimization of a 2-step reaction sequence was accomplished in 3-4 days, with over 200 different reaction conditions evaluated. Combinatorial arrays were performed using the optimized conditions to synthesize 590 new compounds which were tested for inhibition against N-His (D381E) ICE. Thirty-five compounds showed at least a tenfold improvement in activity compared to an initial standard.
MeSH terms
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Amino Acid Substitution
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Aspartic Acid / analogs & derivatives*
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Aspartic Acid / chemical synthesis*
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Aspartic Acid / chemistry
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Aspartic Acid / pharmacology
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Automation
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Caspase Inhibitors*
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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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Drug Design
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Indicators and Reagents
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Ketones / chemical synthesis*
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Ketones / chemistry
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Ketones / pharmacology
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Kinetics
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Molecular Structure
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Structure-Activity Relationship
Substances
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Caspase Inhibitors
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Cysteine Proteinase Inhibitors
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Indicators and Reagents
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Ketones
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Aspartic Acid