Towards Highly-Reactive Pyri(mi)dinol-Based Fluorescent Antioxidant Indicators And Cyclopropane Lipids: Autoxidizability and Potential as Inhibitors of Lipoxygenases

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Yang, Jianxing
pyridinol pyrimidinol antioxidants , lipoxygenase inhibitors , cyclopropane fatty acids , BODIPY
Chapter 2 In solution, py(mi)ridinols 1.33, 1.34 and 1.35 are 2-, 5- and 28-fold more reactive antioxidants, respectively, than α-TOH (the most potent lipid-soluble antioxidant in nature). In order to develop a highly-reactive fluorescent indicator of lipid peroxidation in cells, we sought to couple these antioxidants with boron-dipyrro- methene (BODIPY) dyes, such that the resulting conjugates will display a significant fluorecence enhancement upon oxidation. This chapter details efforts towards the synthesis of these compounds. Chapter 3 Lipoxygenases are a family of important enzymes that catalyze the dioxygenation of arachidonic acid to yield a variety of potent lipid mediators that have been implicated in the pathogenesis of numerous degenerative conditions. We have undertaken a preliminary study of the effect of replacing the unsaturation in the related polyunsaturated lipid linoleic acid with cyclopropane rings on both the oxidizability of the lipid, as well as lipoxygenase’s ability to utilize it as a substrate. We anticipate that these analogs will be useful in co-crystallization studies with the enzyme that will provide unique insight into substrate acquisition, binding and the necessary conformation for catalysis.
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