本项目是应早产治疗的迫切需要，在证实NMBR是子宫平滑肌细胞膜上临产前后显著差异上调的G蛋白偶联受体家族成员，通过P65/c-jun—IL-6/COX-2 启动分娩研究的基础上，发现至今缺乏基于NMBR结构信息设计的特异拮抗剂进行早产干预的研究。因此，本项目拟联合清华大学Brian Kobilka教授实验室，应用超高蛋白得率的sf9昆虫细胞优化表达系统获得足量的NMBR蛋白，联合利用Flag-tag标签与抗体的免疫亲和纯化、金属螯合层析，加上凝胶阻滞层析的方法，获得高纯度的NMBR重组蛋白。进而在脂立方相中培养NMBR/先导化合物晶体，再联合X-射线衍射技术、晶体学软件等进行模型构建，获得NMBR三维结构，并基于结构信息对其拮抗剂进行优化和体内、体外实验的验证。旨在揭示NMBR三维结构和基于其结构信息优化的新一代NMBR拮抗剂，为以NMBR为靶点药物的设计及早产治疗开拓新的思路。

This study is initiated to fulfill the urgent need of preterm treatment. It has been confirmed that NMBR is one of the GPCRs that has significantly up-regulated expression before and after labor on the uterine smooth muscle cell membrane, and NMBR triggers labor onset through P65/c-jun-IL-6/COX-2. It was found that there was a lack of specific antagonists based on the structural information design of NMBR to the premature intervention. Therefore, this study would like to establish joint research with the Kobilka lab at Tsinghua University. We plan to use a high-yield sf9 insect cell expression system to gain sufficient NMBR, and use Flag-tag antibody immunoaffinity purification, metal chelate chromatography, plus size exclusion chromatography to obtain high purity NMBR recombinant protein. We will then co-crystallize the purified NMBR with lead compounds using lipid cubic phase method, construct the model with X-ray diffraction technology plus crystallography software and solve the three-dimensional structure of NMBR. The structure information will be used to guide antagonist optimization and verification of in vivo and in vitro experiments. Our purpose is to reveal the three-dimensional structure of NMBR and to make a new NMBR antagonist based on the optimization of its structural information. This work will shield new insights to the design of drugs targeting NMBR for preterm birth treatment.