Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA.
Bioorg Med Chem. 2012 Jun 15;20(12):3742-5. doi: 10.1016/j.bmc.2012.04.046. Epub 2012 Apr 28.
Four metabolites of okadaic acid were generated by incubation with human recombinant cytochrome P450 3A4. The structures of two of the four metabolites have been determined by MS/MS experiments and 1D and 2D NMR methods using 94 and 133 μg of each metabolite. The structure of a third metabolite was determined by oxidation to a metabolite of known structure. Like okadaic acid, the metabolites are inhibitors of protein phosphatase PP2A. Although one of the metabolites does have an α,β unsaturated carbonyl with the potential to form adducts with an active site cysteine, all of the metabolites are reversible inhibitors of PP2A.
四种 okadaic 酸代谢产物通过与人重组细胞色素 P450 3A4 孵育生成。通过使用 94 和 133 μg 每种代谢产物的 MS/MS 实验和 1D 和 2D NMR 方法，已经确定了其中两种代谢产物的结构。第三种代谢产物的结构通过氧化确定为具有已知结构的代谢产物。与 okadaic 酸一样，这些代谢产物是蛋白磷酸酶 PP2A 的抑制剂。尽管其中一种代谢产物确实具有潜在的α，β不饱和羰基，可能与活性位点半胱氨酸形成加合物，但所有代谢产物均为 PP2A 的可逆抑制剂。
