The effect of "cap" analogs on reovirus mRNA binding to wheat germ ribosomes. Evidence for enhancement of ribosomal binding via a preferred cap conformation.

摘要: A variety of compounds related to the 5'-terminal "cap" (m7GpppN) eukaryotic mRNA's were chemically synthesized and tested as inhibitors reovirus mRNA binding wheat germ ribosomes. Under our conditions ribosomes, 7-methyl-, 7-ethyl-, 7-benzyl-GDP, but not GDP, decreased stable initiation complex formation by 70 80% at a concentration 0.1 mM indicating that 7-substitution, specific substituent, was required for effect. Elimination positive charge on imidazole 7-substituted treatment with alkali destroyed their inhibitory activity. Similarly, reduction 8-hydro-m7GDP reversibly activity m7GDP. The results consistent hypothesis resulting from 7-alkylation provides an active cap conformer via interaction phosphate oxygens positively charged moiety. In accord this suggestion, 7-carboxymethyl GDP 7,8-dimethyl found be less than 2-amino group also important since m7IDP effective m7GDP m7XDP did inhibit ribosome binding. Other poor 6-Cl-m7GDP 1,7-dimethyl N2,7-dimethyl 2'-deoxy-m7GDP, m7GppI had essentially same