Abstract
The proteasome is a multicatalytic proteinase complex which plays a central role in intracellular protein degradation. We report here the synthesis and biological activities of a new class of specific proteasome inhibitors selective for trypsin-like activity. These tripeptide-based compounds bearing a C-terminal vinyl ester are nontoxic, and do not affect cell proliferation, but are able to modulate the generation and presentation of immunogenic peptides presented by MHC class I molecules.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Epitopes
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Esters / chemical synthesis
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Esters / chemistry
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Esters / pharmacology
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HLA-A2 Antigen / metabolism
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Herpesvirus 4, Human / immunology
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Humans
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacology
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Proteasome Inhibitors*
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Structure-Activity Relationship
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T-Lymphocytes, Cytotoxic / immunology
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Trypsin Inhibitors / chemical synthesis*
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Trypsin Inhibitors / chemistry
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Trypsin Inhibitors / pharmacology
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Vinyl Compounds / chemical synthesis*
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Vinyl Compounds / chemistry
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Vinyl Compounds / pharmacology
Substances
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Antineoplastic Agents
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Epitopes
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Esters
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HLA-A2 Antigen
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Oligopeptides
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Proteasome Inhibitors
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Trypsin Inhibitors
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Vinyl Compounds