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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Prof. Todd Marder, Durham University (UK)
Metal Catalyzed Synthesis of Retinoids for Stem Cell Differentiation Including Applications of Novel C-H Bond Functionalization Processes
Retinoids are natural and synthetic molecules structurally and/or functionally analogous to all trans retinoic acid (ATRA).
ATRA, the natural metabolite of Vitamin A, regulates a wide range of essential processes such as mammalian embryogenesis, cellular differentiation, proliferation and apoptosis, amongst others. In vitro use of ATRA is complicated by its isomerization under laboratory conditions, as the different isomers activate different biological processes. In order to overcome this, retinoids stable to heat and light have been developed, and we have shown that they are capable of triggering stem cell differentiation reproducibly, but in different ways, depending on their structure. For example, one synthetic system which appears to be more active than ATRA, and which preliminary evidence suggests may function by the same biological pathways, has been developed and used to trigger differentiation to provide neurons (nerve cells).
The synthetic routes employed to prepare the retinoids will be addressed, which include a variety of cross-coupling procedures. In addition, both aromatic and vinylic C-H bond borylation processes have been combined in a 4-step synthesis of high value retinoid methylesters from simple hydrocarbon precursors. Finally, studies of cell differentiation and preliminary proteomic data will be presented.
D.J. Maltman, V.B. Christie, J.C. Collings, J.H. Barnard, S. Fenyk, T.B. Marder, A. Whiting, and S.A. Przyborski, "Proteomic Profiling of the Stem Cell Response to Retinoic Acid and Synthetic Retinoid Analogues: Identification of Major Retinoid-inducible Proteins," Molecular Biosystems, accepted February 2009.
J.H. Barnard, C.E. Bridgens, A.S. Batsanov, E.B. Cartmell, V.B. Christie, J.C. Collings, T.B. Marder, S.A. Przyborski, and A. Whiting, "Synthesis and Evaluation of Selective Stem Cell Differentiation Agents Based on Synthetic Retinoid Derivatives," Org. Biomol. Chem. 6, 3497-3507 (2008).
V.B. Christie, T.B. Marder, A. Whiting, and S.A. Przyborski, "The Role of Retinoids in the Adult Nervous System and their Theraputic Potential," Mini Reviews in Medicinal Chemistry, 8, 601-608 (2008).
For more information contact Prof. Seth Marder (404) 385-6048.
