title: Synthesis and evaluation of potential inhibitors of eIF4E cap binding to 7-methyl GTP.
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.
authors.affiliation: Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Phalguni
authors.initials: P
authors.lastname: Ghosh
authors.forename: Chunkyung
authors.initials: C
authors.lastname: Park
authors.forename: Mark S
authors.initials: MS
authors.lastname: Peterson
authors.forename: Peter B
authors.initials: PB
authors.lastname: Bitterman
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Polunovsky
authors.forename: Carston R
authors.initials: CR
authors.lastname: Wagner
mesh_terms: 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*
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D012314:RNA Cap Analogs; C017516:7-methylguanosine triphosphate