Abstract
A series of peptidomimetics based on a hydroxyproline scaffold was prepared and evaluated for inhibition of farnesyltransferase and geranylgeranyltransferase I in both enzymatic and cell-based assays. A number of analogs were potent and selective inhibitors of FTase, while one compound (22) was nonselective in the enzymatic assays but eight-fold selective for inhibition of GGTase in the cellular assay (IC50 = 0.39 microM).
MeSH terms
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3T3 Cells / drug effects
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Animals
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Drug Design
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology*
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Hydroxyproline / chemistry*
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Inhibitory Concentration 50
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Methionine / analogs & derivatives
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Methionine / pharmacology
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Mice
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Molecular Mimicry
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Peptides / chemistry*
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Structure-Activity Relationship
Substances
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B 956
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Enzyme Inhibitors
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Peptides
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Methionine
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Alkyl and Aryl Transferases
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geranylgeranyltransferase type-I
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p21(ras) farnesyl-protein transferase
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Hydroxyproline