The effect of "cap" analogs on reovirus mRNA binding to wheat germ ribosomes. Evidence for enhancement of ribosomal binding via a preferred cap conformation
- PMID: 632288
The effect of "cap" analogs on reovirus mRNA binding to wheat germ ribosomes. Evidence for enhancement of ribosomal binding via a preferred cap conformation
Abstract
A variety of compounds related to the 5'-terminal "cap" (m7GpppN) of eukaryotic mRNA's were chemically synthesized and tested as inhibitors of reovirus mRNA binding to wheat germ ribosomes. Under our conditions of mRNA binding to ribosomes, 7-methyl-, 7-ethyl-, and 7-benzyl-GDP, but not GDP, decreased stable initiation complex formation by 70 to 80% at a concentration of 0.1 mM indicating that 7-substitution, but not a specific substituent, was required for the effect. Elimination of the positive charge on the imidazole of the 7-substituted compounds by treatment with alkali destroyed their inhibitory activity. Similarly, reduction to 8-hydro-m7GDP reversibly decreased the activity of m7GDP. The results were consistent with the hypothesis that the positive charge resulting from 7-alkylation provides an active cap conformer for binding via interaction of phosphate oxygens with the positively charged imidazole moiety. In accord with this suggestion, 7-carboxymethyl GDP and 7,8-dimethyl GDP were found to be less inhibitory than m7GDP. A 2-amino group was also important since m7IDP was less effective than m7GDP and 0.1 mM m7XDP did not inhibit ribosome binding. Other poor inhibitors were 6-Cl-m7GDP and 1,7-dimethyl GDP but N2,7-dimethyl GDP, 2'-deoxy-m7GDP, and m7GppI had essentially the same activity as m7GDP.
Similar articles
-
Initiation factors eIF4A and C1 from wheat germ and the formation of mRNA X ribosome complexes.Arch Biochem Biophys. 1985 Apr;238(1):146-53. doi: 10.1016/0003-9861(85)90150-x. Arch Biochem Biophys. 1985. PMID: 3985612
-
A wheat germ cap-site factor functional in protein chain initiation.Arch Biochem Biophys. 1986 May 1;246(2):710-5. doi: 10.1016/0003-9861(86)90327-9. Arch Biochem Biophys. 1986. PMID: 3707129
-
Ribosome binding to reovirus mRNA in protein synthesis requires 5' terminal 7-methylguanosine.Cell. 1975 Oct;6(2):185-95. doi: 10.1016/0092-8674(75)90009-4. Cell. 1975. PMID: 1182800
-
Dependence of translation on 5'-terminal methylation of mRNA.Fed Proc. 1976 Sep;35(11):2214-7. Fed Proc. 1976. PMID: 782922 Review.
-
Inhibitors of protein biosynthesis.Mol Biol Biochem Biophys. 1979;30:i-x, 1-312. doi: 10.1007/978-3-642-81309-2. Mol Biol Biochem Biophys. 1979. PMID: 370549 Review. No abstract available.
Cited by
-
A review: Mechanism of action of antiviral drugs.Int J Immunopathol Pharmacol. 2021 Jan-Dec;35:20587384211002621. doi: 10.1177/20587384211002621. Int J Immunopathol Pharmacol. 2021. PMID: 33726557 Free PMC article. Review.
-
Enzymatic synthesis of RNAs capped with nucleotide analogues reveals the molecular basis for substrate selectivity of RNA capping enzyme: impacts on RNA metabolism.PLoS One. 2013 Sep 25;8(9):e75310. doi: 10.1371/journal.pone.0075310. eCollection 2013. PLoS One. 2013. PMID: 24086504 Free PMC article.
-
Synthesis of N²-modified 7-methylguanosine 5'-monophosphates as nematode translation inhibitors.Bioorg Med Chem. 2012 Aug 1;20(15):4781-9. doi: 10.1016/j.bmc.2012.05.078. Epub 2012 Jun 10. Bioorg Med Chem. 2012. PMID: 22748379 Free PMC article.
-
Emerging therapeutics targeting mRNA translation.Cold Spring Harb Perspect Biol. 2012 Apr 1;4(4):a012377. doi: 10.1101/cshperspect.a012377. Cold Spring Harb Perspect Biol. 2012. PMID: 22474009 Free PMC article.
-
Ribavirin is not a functional mimic of the 7-methyl guanosine mRNA cap.RNA. 2005 Aug;11(8):1238-44. doi: 10.1261/rna.2930805. RNA. 2005. PMID: 16043507 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
