Design and biological evaluation of synthetic retinoids: Probing length vs. stability vs. activity

Graeme Clemens, Kevin R. Flower, Peter Gardner, Andrew P. Henderson, Jonathan P. Knowles, Todd B. Marder, Andrew Whiting, Stefan Przyborski

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    All trans-retinoic acid (ATRA) is widely used to direct the differentiation of cultured stem cells. When exposed to the pluripotent human embryonal carcinoma (EC) stem cell line,, ATRA induces ectoderm differentiation and the formation of neuronal cell types. We report in this study that novel polyene chain length analogues of ATRA require a specific chain length to elicit a biological responses of the EC cells, with synthetic retinoid AH61 being particularly active, and indeed more so than ATRA. The impacts of both the synthetic retinoid AH61 and natural ATRA on the cells were directly compared using both RT-PCR and Fourier Transform Infrared Micro-Spectroscopy (FT-IRMS) coupled with multivariate analysis. Analytical results produced from this study also confirmed that the synthetic retinoid AH61 had biological activity comparable or greater than that of ATRA. In addition to this, AH61 has the added advantage of greater compound stability than ATRA, therefore, avoiding issues of oxidation or decomposition during use with embryonic stem cells. © 2013 The Royal Society of Chemistry.
    Original languageEnglish
    Pages (from-to)3124-3134
    Number of pages10
    JournalMolecular BioSystems
    Issue number12
    Publication statusPublished - Dec 2013


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