Abstract
Peptide-semicarbazones derived from Z-Trp-Trp-Phe-aldehyde inhibit the chymotryptic activity of the human proteasome at nanomolar concentrations, but are less active in a NFkappaB reporter gene assay. Cyclic semicarbazones, in contrast, combine a strong inhibitory effect on the enzyme with an inhibition of NFkappaB signaling in the nanomolar range. In addition, a practical synthesis for scale-up of such compounds was developed.
MeSH terms
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Cell Proliferation / drug effects
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Cells, Cultured
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Humans
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Immunosuppressive Agents / chemical synthesis
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Immunosuppressive Agents / chemistry
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Immunosuppressive Agents / pharmacology
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Structure
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NF-kappa B / metabolism
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Peptides / chemistry*
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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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Proteasome Endopeptidase Complex / chemistry
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Proteasome Endopeptidase Complex / metabolism*
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Proteasome Inhibitors*
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Semicarbazones / chemical synthesis*
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Semicarbazones / chemistry
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Semicarbazones / pharmacology*
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Sensitivity and Specificity
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Signal Transduction / drug effects
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Structure-Activity Relationship
Substances
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Immunosuppressive Agents
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NF-kappa B
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Peptides
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Protease Inhibitors
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Proteasome Inhibitors
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Semicarbazones
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Proteasome Endopeptidase Complex