兼具nNOS-Capon解偶联和抗氧化活性的双重神经保护剂的设计、合成及生物活性评价

缺血性脑卒中是世界上最主要的致残和致死疾病之一。NMDAR-PSD95-nNOS-Capon信号通路在神经兴奋性毒性的传递中起重要作用，解开nNOS-Capon的偶联具有神经保护作用。另外，缺血及再灌注过程中产生的大量自由基加速神经细胞的死亡。SS-31（D-Arg-Dmt-Lys-Phe-NH2）是稳定的、能通过血脑屏障的、具有Tat样功能的四肽分子，该肽具有显著的抗氧化活性和药物载体功能。在本研究中，我们计划设计并合成SS-31缀合的Capon羧基末端分子，这样的分子具有nNOS-Capon解偶联的神经保护作用，且具有抗氧化的神经保护活性。对合成的化合物进行生物活性研究，得到具有优良神经保护作用的先导化合物，为获得具有自主知识产权的全新神经保护剂打下基础。

Ischemic stroke is one of the most leading disabling and lethal diseases in the world. The NMDAR-PSD95-nNOS-Capon signaling pathway plays an important role in the transmission of nerve excitotoxicity, and the uncoupling of nNOS-Capon has a neuroprotective effect. In addition, the body generates a large number of free radicals to accelerate the death of nerve cells in the process of ischemia and reperfusion. SS-31 (D-Arg-Dmt-Lys-Phe-NH2), with similar function of Tat, is a stable tetrapeptide, which can go through the blood-brain barrier. SS-31 has a significant antioxidant activity, which is also used as drug carrier. In this study, some SS-31-Capon conjugates are designed and synthesized to get potential neuroprotective drugs which display the nNOS-Capon uncoupling effect and antioxidant activity. The lead compounds will be assayed to get some potent neuroprotective agents, which will lay a good foundation for obtaining some new neuroprotective drugs with independent intellectual property rights.