Study on the Enzyme Action Mechanism in the Phospholipid Hydrolysis by Means of small Molecular Inhibitors

Phospholipids被分类为glycerophospholipids和sphingophospholipids。对于the metabolism of unsaturated fatty acids，对于the hydrolysis of the ester linkage at the sn-2 position of gly？ophospholipids and responsibles for the metabolism of unsaturated fatty acids。一方面，鞘瘤酶是酶的一般术语，其中磷酸酶链中磷脂酶的羟基连接到生产谷氨酰胺，被称为哺乳动物细胞膜中的脂质秒信使。我们发现3-甲氧碳基-2，4，6-三烯（A）强不激活的磷脂酶A-D22-D2从bovine Pancreas中分离。The inactivation Mechanism of PLA y D22 y D2 by the compound A was elucidated by means of the stereocontrolled synthesis of the derivatives of A， structure activity relationship， amino acid analysis of the complex with PLA y D22 y D2， and model reactions with amines。所以，这个化合物被找到了一个选择性的修改的Lys-56其中包括在内。 ... More interfacial recognition site of bovine pancreatic PLA-D22-D2， by the MALDI-TOF-Mass peptide mapping analyses of the complex.We also synthesized the new cyclic amide analog as the second-generation inhibitor having an oxazolidinone ring， because we previously synthesized the oxazolidinone phospholipid analog which competitively acted on the catalytic site of PLA-D22-On the other hand， in the study of Sphingomyelinase，我们在（D）-神经胶质细胞中实现了有效的合成，并在（D）-神经胶质细胞中找到了一种重要的合成，作为鞘瘤酶和后骨骨骼中的双键不是B的水合作用的必要条件。Cereus sphingomyelinase。Furthermore，我们研究了鞘氨酰亚胺甲基化和甲基化类似物的立体控制有效综合症，是第一个基底-模拟抑制剂，也是它们实际抑制了酶的氢化能力。这些模拟抑制剂可能是有用的，用于鞘氨酰酶氢化机制的诱导。Less（低）

Phospholipids are classified into glycerophospholipids and sphingophospholipids. Phospholipase AィイD22ィエD2 (PLAィイD22ィエD2) catalyzes the hydrolysis of the ester linkage at the sn-2 position of glycerophospholipids and responsibles for the metabolism of unsaturated fatty acids. Meanwhile, sphingomyelinase is the general term of the enzyme which catalyzes the hydrolysis of the phosphoester linkage of sphingomyelin to produce ceramide, which has been known as a lipid second messenger in mammalian cell membranes.We found that 3-methoxycarbonyl-2, 4, 6-trienal (A) strongly inactivated phospholipase AィイD22ィエD2 which was isolated from bovine pancreas. The inactivation mechanism of PLAィイD22ィエD2 by the compound A was elucidated by means of the stereocontrolled synthesis of the derivatives of A, structure activity relationship, amino acid analysis of the complex with PLAィイD22ィエD2, and model reactions with amines. Thus, the compound A was found to selectively modify Lys-56 which is included in the … More interfacial recognition site of bovine pancreatic PLAィイD22ィエD2, by the MALDI-TOF-Mass peptide mapping analyses of the complex.We also synthesized the new cyclic amide analog as the second-generation inhibitor having an oxazolidinone ring, because we had previously synthesized the oxazolidinone phospholipid analog which competitively acted on the catalytic site of PLAィイD22ィエD2.On the other hand, in the study of sphingomyelinase, we achieved the efficient synthesis of (D)-erythro-sphigomyelin, and found that (D)-erythro stereochemistry is essentially important as the substrate for sphingomyelinase and the double bond in the backbone skeleton was not essential for the hydrolysis by B. cereus sphingomyelinase. Furthermore, we established the stereocontrolled efficient synthesis of sphingomyelin methylene and ethylene analogs, which are the first substrate-analog inhibitors, and they actually inhibited the hydrolytic ability of the enzyme. These analog inhibitors might be useful for the elucidation of the sphingomyelinase hydrolytic mechanism. Less