Study on the development of molecules for depressing neuropathic pain based on tertiary structure of human P2X4 receptor

我们计划开发P2X4受体参与的抑制神经病理性疼痛的分子。 由于我们制备了与大鼠P2X4胞外区结合的单克隆抗体，我们计划使用类似的方法制备与人P2X4胞外区结合的单克隆抗体。 尽管制备了几种类型的结合人P2X4胞外区的单克隆抗体，但它们不具有抑制神经性疼痛的潜力。 我们新开发的方法来评估的单克隆抗体与功能三聚体P2X4受体的相互作用。使用该方法，显示在本研究中制备的单克隆抗体不结合功能性三聚体P2X4受体，这可能是结合人P2X4胞外区的单克隆抗体不具有抑制神经性疼痛的潜力的原因。

We planed to develop molecules for depressing neuropathic pain involved in P2X4 receptor. Since we prepared a monoclonal antibody bound to rat P2X4 extracellular region, we planed to prepare monoclonal antibodies bound to human P2X4 extracellular regions using similar methods. Although a couple of types of monoclonal antibodies bound to human P2X4 extracellular regions were prepared, they did not have a potential to depress neuropathic pain. We newly developed the method to evaluate the interaction of a monoclonal antibody with a functionally trimeric P2X4 receptor. Using the method, it was shown that prepared monoclonal antibodies prepared in this study did not bind to a functionally trimeric P2X4 receptor, which may be the reason why monoclonal antibodies bound to human P2X4 extracellular regions did not have a potential to depress neuropathic pain.