Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP.
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.
Ghosh
Phalguni
P
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Park
Chunkyung
C
Peterson
Mark S
MS
Bitterman
Peter B
PB
Polunovsky
Vitaly A
VA
Wagner
Carston R
CR
D016475:3T3 Cells; D000818:Animals; D001667:Binding, Competitive; D004353:Drug Evaluation, Preclinical / Q000379:methods; D039561:Eukaryotic Initiation Factor-4E / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding / Q000502:physiology; D012314:RNA Cap Analogs / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D039561:Eukaryotic Initiation Factor-4E; D012314:RNA Cap Analogs; C017516:7-methylguanosine triphosphate