Core F(B): Synthesis Design

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The Lipid Synthesis Core (Core F) will serve the LIPID MAPS Consortium by providing synthetic chemistry support for the Lipidomic Core groups. Core F is composed of two sub-Cores: Lipid Standards, F(A) and Synthesis Design, F(B). The Lipid Standards sub-Core is represented by Avanti Polar Lipids, Inc. This sub- Core will serve as the manufacturing arm of the LIPID MAPS consortium, and as such has the responsibility to (a) design and execute synthetic routes to novel lipids discovered by the consortium, (b) produce novel agonists, such as Kdo2-Lipid A, (c) produce lipid products that can be used as internal standards, such as stable isotope-labeled compounds and compounds containing odd chain fatty acids, (d) produce lipid products that can be used as primary mass spectrometric standards, such as synthetic analogues of natural products, (e) develop packaging for mass spectrometric standards with defined concentrations and maximum shelf life, (f) develop production scale synthesis of the LDL oxidized lipid mimetic developed by Core F(B), and (g) continue the production and stability testing of products developed in the previous grant period. All of the compounds manufactured and characterized will be made available to the consortium members at no charge, while the larger lipid community will have access to these products through the Avanti catalog. The Synthesis Design sub-Core will develop synthetic pathways for novel lipid compounds including the active agent present in oxidized LDL and odd-carbon chain fatty acids with varying degrees of unsaturation. Core F(B) will work closely with the Lipid Standards sub-Core to develop production scale manufacturing processes for these compounds. The successful completion of the proposed specific aims of Core F will ensure that the Lipidomic Core groups have pure, stable compounds, which are essential to the completion of the overall objectives of the Consortium. In essence, the lipid standards provided by Core F are the foundations on which the research proposed by the other Core laboratories is based.