A spectroscopic study of the binding of N-7-substituted cap analogues to human protein synthesis initiation factor 4E.
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.
Carberry
S E
SE
Department of Chemistry, Hunter College, City University of New York, New York 10021.
Darzynkiewicz
E
E
Stepinski
J
J
Tahara
S M
SM
Rhoads
R E
RE
Goss
D J
DJ
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
D003432:Cross-Linking Reagents; D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D012314:RNA Cap Analogs; D012315:RNA Caps