Development of biotin-retinoid conjugates as chemical probes for analysis of retinoid function.
Fiche publication
Date publication
juin 2018
Journal
Bioorganic & medicinal chemistry letters
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GRONEMEYER Hinrich, Dr MENDOZA Manuel
Tous les auteurs :
Fujii S, Mori S, Kagechika H, Mendoza Parra MA, Gronemeyer H
Lien Pubmed
Résumé
Herein, we report the rational design, synthesis and biological evaluation of conjugates consisting of the synthetic retinoid Am580 and biotin connected via a linker moiety. We found that the linking substructure between the retinoid part and the biotin part is critical for retaining the biological activity. Conjugate 4 with a shorter linker showed similar potency to endogenous retinoid ATRA (1) and the parent compound Am580 (2) for neural differentiation of mouse embryotic carcinoma P19 cells, and showed the same pattern of induction of gene expression. It is expected to be useful as a probe for investigations of retinoid function. The design rationale and structure-activity relationship of the linker moiety are expected to be helpful for developing biotin conjugates of other nuclear receptor ligands.
Mots clés
Biotin conjugate, Chem-seq, Neural differentiation, P19 cells, Retinoid
Référence
Bioorg. Med. Chem. Lett.. 2018 Jun 6;: