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Bioorg Med Chem Lett. 2018 Aug 1;28(14):2442-2445. doi: 10.1016/j.bmcl.2018.06.011. Epub 2018 Jun 6.

Development of biotin-retinoid conjugates as chemical probes for analysis of retinoid function.

Author information

1
Institute for Quantitative Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. Electronic address: fujiis@iam.u-tokyo.ac.jp.
2
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
3
Department of Functional Genomics and Cancer, Institute of Genetics and Molecular and Cellular Biology, (IGBMC), Centre National de la Recherche Scientifique UMR7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, BP 10142, Illkirch Cedex 67404, France. Electronic address: marco@igbmc.fr.
4
Department of Functional Genomics and Cancer, Institute of Genetics and Molecular and Cellular Biology, (IGBMC), Centre National de la Recherche Scientifique UMR7104, Institut National de la Santé et de la Recherche Médicale U964, Université de Strasbourg, BP 10142, Illkirch Cedex 67404, France.

Abstract

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.

KEYWORDS:

Biotin conjugate; Chem-seq; Neural differentiation; P19 cells; Retinoid

PMID:
29908657
DOI:
10.1016/j.bmcl.2018.06.011
[Indexed for MEDLINE]

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