The Organic Synthesis Core (Core C) will provide essential chemistry support for this research program through the synthesis and characterization of novel specialized pro-resolving mediators (SPM) and their sulfido-conjugates (SPM-SC). The Core will be responsible for the total synthesis of a panel of novel SPMs and related SPM probes, including: resolvins, maresins, sulfido-conjugates, and other related molecules that will be studied under this program. Core C will develop and utilize effective stereocontrolled synthetic pathways for the total synthesis of the targeted SPM in stereochemically pure form, and establish suitable methods for their detailed purification and structural verification using spectroscopic techniques. Core C will also prepare needed quantities (up to mg scale) of selected SPM, and will pursue the design and synthesis of selected derivatives that will enable their biological investigation. Core C will also prepare isotopically substituted SPM derivatives to serve as SPM probes for lipidomic profiling in collaboration with Core B and Project 1, 2, and 3, while other SPM probes will serve as precursors of radiolabelled derivatives for mechanistic studies. Finally, Core C will collaborate with Projects 1, 2 and 3 and Cores A-B on the proposed studies involving novel biological actions and cellular mechanisms of SPMs. Overall, these collaborative investigations will help elucidate key unexplored functions of SPMs, and will help validate their functional role(s) in the resolution of inflammation and tissue regeneration.
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