Phosphorylation of enkephalins enhances their proteolytic stability
Phosphorylation of enkephalins enhances their proteolytic stability
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DOI：
10.1016/0024-3205(96)00057-4
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发表时间：
1996-02-23
期刊：
影响因子：
6.1
通讯作者：
Mahalakshmi, P
中科院分区：
文献类型：
--
作者：
Dass, C;Mahalakshmi, P
脑啡肽作为阿片肽的药理作用是有限的，因为它们被内切蛋白酶快速降解。在这项研究中使用了一种新的方法来延长这些肽的寿命。发现N-末端酪氨酸残基的磷酸化对改善[Met]脑啡肽和[Leu]脑啡肽抵抗氨肽酶M作用的稳定性具有深远的影响。然而，当在37 ℃下与纯化的氨肽酶M（EC 3.4.11.2;底物：酶= 1：0.1）在Tris缓冲液（pH 7.02）中孵育时，[Met]脑啡肽和[Leu]脑啡肽的分解在不到1分钟内基本上完全，在孵育开始后60分钟仍检测到相应的磷酸类似物。磷酸-[Met]脑啡肽和磷酸[Leu]脑啡肽的消失速率遵循一级动力学，半衰期分别为7.3和8.8 min。
Pharmacological action of enkephalins as opioid peptides is limited because of their rapid degradation by endoproteases. A novel approach is used in this study to prolong the life of those peptides. Phosphorylation of N-terminal tyrosine residue is found to have a profound influence in improving the stability of [Met]enkephalin and [Leu]enkephalin against the action of aminopeptidase M. Whereas, breakdown of [Met]enkephalin and [Leu]enkephalin is essentially complete in less than one min when incubated at 37 degrees C with purified aminopeptidase M (EC3.4.11.2; substrate:enzyme = 1:0.1) in Tris buffer (pH 7.02), the corresponding phospho analogs are still detected 60 min after start of incubation. The rate of disappearance of phospho-[Met]enkephalin and phospho[Leu]enkephalin follows first-order kinetics with half-lives of 7.3 and 8.8 min, respectively.