Synthesis of 7-benzylguanosine cap-analogue conjugates for eIF4E targeted degradation

摘要

Eukaryotic translation initiation factor 4E (eIF4E) is a key player in the initiation of cap-dependent translation through recognition of the m(7)GpppX cap at the 5' terminus of coding mRNA5. As eIF4E overexpression has been observed in a number of human diseases, most notably cancer, targeting this oncogenic translation initiation factor has emerged as a promising strategy for the development of novel anti-cancer therapeutics. Toward this end, in the present study, we have rationally designed a series of Bn(7)GxP-based PROTACs for the targeted degradation of eIF4E. Herein we describe our synthetic efforts, in addition to biochemical and cellular characterization of these compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.