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

ABSTRACT: Eukaryotic translation initiation factor 4E (eIF4E) is a key player in the initiation of cap-dependent translation through recognition of the m7GpppX cap at the 5' terminus of coding mRNAs. 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 Bn7GxP-based PROTACs for the targeted degradation of eIF4E. Herein we describe our synthetic efforts, in addition to biochemical and cellular characterization of these compounds.

SUBMITTER: Kaur T

PROVIDER: S-EPMC6392074 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Kaur Tanpreet T Menon Arya A Garner Amanda L AL

European journal of medicinal chemistry 20190131

Eukaryotic translation initiation factor 4E (eIF4E) is a key player in the initiation of cap-dependent translation through recognition of the m<sup>7</sup>GpppX cap at the 5' terminus of coding mRNAs. 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 d ...[more]

PMID: 30735900

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