4dum

Publication Abstract from PubMed

Abstract The eukaryotic initiation factor 4E (eIF4E) plays a central role in the initiation of gene translation and subsequent protein synthesis by binding the 5' terminal mRNA cap structure. We designed and synthesized a series of novel compounds display potent binding affinity against eIF4E despite their lack of a ribose moiety, phosphate, and positive charge as present in m7-GMP. The biochemical activity of compound 33 is 95 nM for eIF4E in an SPA binding assay. More importantly, the compound has an IC50 of 2.5 M for inhibiting cap-dependent mRNA translation in a rabbit reticular cell extract assay (RRL-IVT). This series of potent, truncated analogues could serve as a promising new starting point towards the design of neutral eIF4E inhibitors with physicochemical properties suitable for cellular activity assessment.

Structure-guided design, synthesis and evaluation of guanine-derived inhibitors of the eIF4E mRNA-cap interaction.,Chen X, Kopecky D, Mihalic J, Jeffries S, Min X, Heath J, Deignan J, Sujen L, Fu Z, Guimaraes C, Li S, Johnstone S, Xu H, Cardozo M, Shen W, Walker N, Kayser F, Wang Z J Med Chem. 2012 Mar 29. PMID:22458568^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.