The structure-function relationship between peptide aldehyde derivatives on initiation of neurite outgrowth in PC12h cells
The structure-function relationship between peptide aldehyde derivatives on initiation of neurite outgrowth in PC12h cells
复制标题
肽醛衍生物对 PC12h 细胞神经突生长起始的结构-功能关系
DOI：
10.1016/0304-3940(90)90153-z
复制
发表时间：
1990
影响因子：
2.5
通讯作者：
S. Kawashima
中科院分区：
文献类型：
--
作者：
Yumiko Saito;Satoshi Tsubuki;H. Ito;S. Kawashima
我们以前已经表明，在许多蛋白酶抑制剂检查，只有亮抑酶肽类似物，Ac-Leu-Leu-Nle-al（ALLNal），诱导PC 12 h细胞中的神经突生长。由于这种神经突生长在形态和持久性方面不同于神经生长因子（NGF）诱导的神经突生长，因此预期存在调节PC 12 h细胞中神经突形成的特异性蛋白酶。合成了一组10种ALLNal类似物肽蛋白酶抑制剂，并检查了它们在PC 12 h细胞中诱导神经突生长的效力。用苄氧羰基（Z）取代ALLNal中的N-末端乙酰基残基使活性增加约4倍。对于Z-Leu-Leu-X-al，在X残基处诱导神经突生长的顺序为：Leu > Phe > Nva >瓦尔= Ile = Nle > Ala > Gly。Z-Leu-Leu-Leu-al（ZLLLal）的效力比ALLNal强50倍。ZLLLal为表征这种新型蛋白酶提供了强有力的工具。
We have previously shown that, among many protease inhibitors examined, only a leupeptin analogue, Ac-Leu-Leu-Nle-al (ALLNal), induces neurite outgrowth in PC12h cells. Since this neurite outgrowth is different from that induced by nerve growth factor (NGF) in terms of morphology and persistance, the existence of a specific protease which regulates neurite formation in PC12h cells was expected. A set of 10 ALLNal analogue peptide protease inhibitors was synthesized and examined for their potency in inducing neurite outgrowth in PC12h cells. Substitution of the N-terminal acetyl residue in ALLNal by benzyloxycarbonyl (Z) increased the activity by about 4 times. For Z-Leu-Leu-X-al, neurite outgrowth was induced in the following order: Leu > Phe > Nva > Val = Ile = Nle > Ala > Gly at the X residue. The potency of Z-Leu-Leu-Leu-al (ZLLLal) was 50-fold stronger than that of ALLNal. ZLLLal provides a strong tool for characterizing this new type of protease.