Abstract
A set of synthetic approaches was developed and applied to the synthesis of eight frame-shifted isoprenoid diphosphate analogues. These analogues were designed to increase or decrease the methylene units between the double bonds and/or the pyrophosphate moieties of the isoprenoid structure. Evaluation of mammalian GGTase-I and FTase revealed that small structural changes can result in substantial changes in substrate activity.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Alkyl and Aryl Transferases / antagonists & inhibitors*
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Alkyl and Aryl Transferases / metabolism
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Diphosphates / chemical synthesis
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Diphosphates / chemistry
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Diphosphates / pharmacology*
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Farnesyltranstransferase / antagonists & inhibitors*
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Farnesyltranstransferase / metabolism
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Molecular Structure
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Terpenes / chemical synthesis
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Terpenes / chemistry
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Terpenes / pharmacology*
Substances
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Diphosphates
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Enzyme Inhibitors
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Terpenes
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Alkyl and Aryl Transferases
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geranylgeranyltransferase type-I
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Farnesyltranstransferase