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

Clemens, G.; Flower, K.R.; Gardner, P.; Henderson, A.P.; Knowles, J.P.; Marder, T.B.; Whiting, A.; Przyborski, S.A.

doi:10.1039/c3mb70273a

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

Clemens, G.; Flower, K.R.; Gardner, P.; Henderson, A.P.; Knowles, J.P.; Marder, T.B.; Whiting, A.; Przyborski, S.A.

Authors

G. Clemens

K.R. Flower

P. Gardner

A.P. Henderson

J.P. Knowles

T.B. Marder

Professor Andrew Whiting andy.whiting@durham.ac.uk
Emeritus Professor

Professor Stefan Przyborski stefan.przyborski@durham.ac.uk
Executive Dean

Abstract

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, TERA2.cl.SP12, 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 TERA2.cl.SP12, 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 TERA2.cl.SP12 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.

Citation

Clemens, G., Flower, K., Gardner, P., Henderson, A., Knowles, J., Marder, T., …Przyborski, S. (2013). Design and biological evaluation of synthetic retinoids: Probing length vs. stability vs. activity. Molecular bioSystems, 9(12), 3124-3134. https://doi.org/10.1039/c3mb70273a

Journal Article Type	Article
Publication Date	Dec 1, 2013
Deposit Date	Nov 22, 2013
Publicly Available Date	May 22, 2014
Journal	Molecular BioSystems
Print ISSN	1742-206X
Electronic ISSN	1742-2051
Publisher	Royal Society of Chemistry
Peer Reviewed	Peer Reviewed
Volume	9
Issue	12
Pages	3124-3134
DOI	https://doi.org/10.1039/c3mb70273a