Mechanisms of action of emodepside.
Mechanisms of action of emodepside.
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DOI：
10.1007/s00436-005-1438-z
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发表时间：
2005-10-01
影响因子：
2
通讯作者：
Wunderlich, F
中科院分区：
文献类型：
--
作者：
Harder, A;Holden-Dye, L;Wunderlich, F
环八肽类化合物的研究始于20世纪90年代初。PF1022A是emodepside的起始物质，是山茶花（Camellia japonica）叶片微生物群中菌丝体（Mycelia sterilia）的天然次生代谢物。PF1022A由四种n -甲基-l -亮氨酸、两种d -乳酸和两种d -苯乳酸组成，它们构成了一个交替的l- d -l结构的环八肽。Emodepside是PF1022A的半合成衍生物，它包含一个在两个d -苯基乳酸的对位上连接的morpholine。Emodepside对多种胃肠道线虫有效。在线虫中，Emodepside与突触前嗜碱蛋白受体结合。以下突触前信号转导通过gqα蛋白和磷脂酶- cβ的激活发生，从而导致二酰基甘油（DAG）的动员。DAG随后激活UNC-13和synaptobrevin，这两种蛋白在突触前囊泡功能中起重要作用。这最终导致了一个目前身份不明的发射器的释放。递质（或调节剂）在突触后膜发挥作用，诱导线虫咽部和躯体肌肉组织的弛缓性麻痹。
The research of the class of cyclic octadepsipeptides started at the beginning of the 1990s. PF1022A, the starting material of emodepside, is a natural secondary metabolite of the fungus Mycelia sterilia, which belongs to the microflora of the leaves of Camellia japonica. PF1022A consists of four N-methyl-L-leucins, two D-Iactic acids and two D-phenyllactic acids, which build up a cyclic octadepsipeptide with an alternating L-D-L-configuration. Emodepside is a semisynthetic derivative of PF1022A, which contains a morpholine attached in para position at each of both D-phenyllactic acids. Emodepside is efficacious against a variety of gastrointestinal nematodes. Emodepside binds to a presynaptic latrophilin receptor in nematodes. The following presynaptic signal transduction occurs via activation of Gqalpha protein and phospholipase-Cbeta, which leads to mobilization of diacylglycerol (DAG). DAG then activates UNC-13 and synaptobrevin, two proteins which play an important role in presynaptic vesicle-functioning. This finally leads to the release of a currently unidentified transmitter. The transmitter (or modulator) exerts its effects at the postsynaptic membrane and induces a flaccid paralysis of the pharynx and the somatic musculature in nematodes.