Abstract
Successful biochemical studies of the natural products belactosin A and C as well as their more stable acylated derivatives have proved them to be powerful proteasome inhibitors and thereby potential candidates as pharmacologically relevant active compounds. In order to understand their structure-biological activity relations in detail and to find ways of improving their biological activity, four new modified belactosin congeners have been synthesized and tested. One of them (compound 6) turned out to be a more potent inhibitor against HeLa cells than the known proteasome inhibitor MG132.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acylation
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Animals
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Antineoplastic Agents
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Blotting, Western
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Crystallography, X-Ray
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Cysteine Proteinase Inhibitors / pharmacology*
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Dose-Response Relationship, Drug
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Female
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Fibroblasts / cytology
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Fibroblasts / drug effects*
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HeLa Cells
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Humans
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Leupeptins / pharmacology
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Mice
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Mice, Transgenic
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Models, Molecular
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Molecular Structure
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Peptides / chemical synthesis*
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Peptides / pharmacology
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Proteasome Endopeptidase Complex / metabolism
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Proteasome Inhibitors*
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Stereoisomerism
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Structure-Activity Relationship
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Uterine Cervical Neoplasms / drug therapy*
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Uterine Cervical Neoplasms / pathology
Substances
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Antineoplastic Agents
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Cysteine Proteinase Inhibitors
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Leupeptins
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Peptides
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Proteasome Inhibitors
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belactosin C
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Proteasome Endopeptidase Complex
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benzyloxycarbonylleucyl-leucyl-leucine aldehyde