Analysis of PPARr-fatty acids interaction

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To understand interaction of PPARr and fatty acids, We applied several techniques, including organic synthesis, X-ray crystallization, crystallographic analysis, protein NMR spectroscopy and in silico analysis. The results of those experiments will follow(1) We synthesized very-long-chain polyunsaturated fatty acids and oxidized those derivatives.(2) We obtained co-crystal of PPARr and synthesized fatty acids and solved those structures, which indicates both 5-oxoTrHA and 6-oxoTHA afforded1,6-conjugate adducts. On the other hand, 6-oxoTHA makes extra cavity in PPARr ligand binding pocket.(3) ESI experiment indicates that reactivity of conjugate addition depends on positioning of conjugated double bond.(4) NMR experiment revealed that partial agonist 4-oxoDHA moderately shifted residues on helix12 compare to shift of a full agonist.(5) Those results were verified using modeling software SYBYL