Lookup NU author(s): Veronica Christie,
Dr Caroline Bridgens,
Dr Chris Redfern,
Professor Todd Marder
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All-trans-retinoic acid (ATRA) and its associated analogues are important mediators of cell differentiation and function during the development of the nervous system. It is well known that ATRA can induce the differentiation of neural tissues from human pluripotent stem cells. However, it is not always appreciated that ATRA is highly susceptible to isomerisation when in solution, which can influence the effective concentration of ATRA and subsequently its biological activity. To address this source of variability, synthetic retinoid analogues have been designed and synthesised that retain stability during use and maintain biological function in comparison to ATRA. It is also shown that subtle modifications to the structure of the synthetic retinoid compound impacts significantly on biological activity, as when exposed to cultured human pluripotent stem cells, synthetic retinoid 4-(5,5,8,8-tetramethyl-5,6,7,8- tetrahydronaphthalen-2-ylethynyl)benzoic acid, 4a (para-isomer), induces neural differentiation similarly to ATRA. In contrast, stem cells exposed to synthetic retinoid 3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-ylethynyl)benzoic acid, 4b (meta-isomer), produce very few neurons and large numbers of epithelial-like cells. This type of structure-activity-relationship information for such synthetic retinoid compounds will further the ability to design more targeted systems capable of mediating robust and reproducible tissue differentiation. © 2008 The Royal Society of Chemistry.
Author(s): Christie V, Barnard J, Batsanov A, Bridgens C, Cartmell E, Collings J, Maltman D, Redfern CPF, Marder T, Przyborski S, Whiting A
Publication type: Article
Publication status: Published
Journal: Organic and Biomolecular Chemistry
Print publication date: 01/01/2008
ISSN (print): 1477-0520
ISSN (electronic): 1477-0539
Publisher: Royal Society of Chemistry
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