Abstract
Cap-dependent translation is initiated by the binding of eIF4E to capped mRNA (m(7)GpppN). We have prepared a small library of 7-methyl guanosine nucleoside and nucleotide analogs and evaluated their ability to inhibit eIF4E binding to 7-methyl GTP with a competitive eIF4E binding immunoassay. 5'-H-Phosphonate derivatives in which the 2'- and 3'-riboside hydroxyls were tethered together by an isopropylidene group were shown to be a new class of inhibitors of eIF4E binding to capped mRNA.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Animals
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Binding, Competitive
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Drug Evaluation, Preclinical / methods
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Eukaryotic Initiation Factor-4E / antagonists & inhibitors*
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Eukaryotic Initiation Factor-4E / metabolism*
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Mice
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Protein Binding / physiology
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RNA Cap Analogs / antagonists & inhibitors*
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RNA Cap Analogs / metabolism*
Substances
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Eukaryotic Initiation Factor-4E
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RNA Cap Analogs
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7-methylguanosine triphosphate