title: A spectroscopic study of the binding of N-7-substituted cap analogues to human protein synthesis initiation factor 4E.
abstract: The binding of N-7-substituted cap analogues to eIF-4E from human erythrocytes is described. Data presented here indicate that there is a correlation between the tightness of binding of these cap analogues to eIF-4E and their potency as inhibitors of protein synthesis. This result indicates that the inhibitory activity of the cap analogues is strictly a function of the affinity of the analogue for eIF-4E under equilibrium conditions. The pH dependence of binding of the cap analogues to eIF-4E indicates that the enolate form of the cap is preferred, as originally postulated by Rhoads et al. [(1983) Biochemistry 22, 6084-6088]. Data indicate that there are differences in the mode of binding of alkyl-substituted and aryl-substituted cap analogues to eIF-4E arising from favorable interactions of the phenyl ring with the guanosine moiety. These differences may explain the enhanced recognition of the aryl-substituted cap analogues by eIF-4E.
authors.affiliation: Department of Chemistry, Hunter College, City University of New York, New York 10021.
authors.forename: S E
authors.initials: SE
authors.lastname: Carberry
authors.forename: E
authors.initials: E
authors.lastname: Darzynkiewicz
authors.forename: J
authors.initials: J
authors.lastname: Stepinski
authors.forename: S M
authors.initials: SM
authors.lastname: Tahara
authors.forename: R E
authors.initials: RE
authors.lastname: Rhoads
authors.forename: D J
authors.initials: DJ
authors.lastname: Goss
mesh_terms: D003432:Cross-Linking Reagents; D004912:Erythrocytes / Q000032:analysis; D039561:Eukaryotic Initiation Factor-4E; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D010448:Peptide Initiation Factors / Q000096:biosynthesis; D012314:RNA Cap Analogs; D012315:RNA Caps; D013050:Spectrometry, Fluorescence
chemical_list: D003432:Cross-Linking Reagents; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D012314:RNA Cap Analogs; D012315:RNA Caps