The Chemistry Core provides chemical services and logistical support to the constituent Program Project laboratories. Its primary responsibilities include: (1) The preparation of labeled and unlabeled eicosanoids, standards, analogs, and inhibitors in sufficient quantities for use in biological studies, as assay standards, for structural and/or stereochemical elucidations, and for methodology development. In light of the limited availability of most eicosanoids from natural sources, the synthetic and analytical resources of the Core are essential for the successful conduct of the Program Project. The majority of syntheses are patterned on synthetic routes developed in Project VI or adapted from the literature. Generally, it is necessary to make modifications to the syntheses to accommodate the increased scale of the reactions or to permit the incorporation of labeled atoms. For the latter, commercially labeled fatty acids are convenient precursors or labeled reagents such as [ 2H,3H,18O]-H20, [14C]-NaCN, [2H,3H]-H2 gas, and [2H,3H]-LiAIH4/NaH4 are used. Appropriate analytical techniques, e.g., capillary GC, CE, HPLC, NMR, and mass spectroscopy, ensure product identity, purity, and isotopic composition (if present). (2) Development and validation of analytical techniques for the identification, stereochemical confirmation, and quantification of renal eicosanoids. In particular, electron capture, fluorescence, and chiral capillary electrophoresis protocols will be studied to improve detection sensitivity, attain better resolution, and characterize stereochemistry. As in the past, collaborative development of ELISA assays will be pursued since most renal eicosanoids lack a chromophore suitable for detection and quantification. (3) Provide for the storage, quality assurance, packaging, and distribution of eicosanoids, inhibitors, analogs, reagents, and antibodies to collaborating laboratories.
Showing the most recent 10 out of 376 publications
