随着社会的发展，焦虑症患者日渐增多。目前临床上的抗焦虑药物存在毒副作用大或起效慢的缺点。因此，作用于新靶点、具有新作用机制抗焦虑药物的研制具有重要意义。在前期研究中我们发现并确证了一个治疗焦虑的新靶点，即解开nNOS-Capon的偶联具有抗焦虑作用，针对nNOS PDZ结构域结合位点设计的化合物N-(2-甲氧羰基乙酰基)-D-缬氨酸甲酯（ZLc-002）能够有效抑制nNOS-Capon的偶联，海马定点注射以及静脉给药，ZLc-002在动物模型上均显示显著的抗焦虑作用。本研究以此为基础，对ZLc-002进行结构改造，以提高其生物活性，并进行基于Capon羧基末端二肽A-V、四肽E-I-A-V 及nNOS PDZ 结构域肽库筛选最优序列G-D/E-X-V的拟肽及非肽小分子的设计、合成和生物活性研究，筛选具有良好抗焦虑活性的先导化合物，为获得具有自主知识产权的全新抗焦虑药物打下良好基础。

With the development of society, the stress from society, life and work becomes more and more heavy, patients with anxiety disorder are increasing. However, the present clinical anxiolytic drugs have various side effect and/or slow efficacy. Therefore, development of drugs acting at new target with new mechanism is very important and is of great significance. We found and verified a new target for anxiety, that is uncoupling the interaction of nNOS-Capon showing significantly anxiolytic effect, furthermore, we found that N-(2-carbomethoxyacetyl)-D-valine methyl ester (ZLc-002) could effectively uncouple the association of nNOS-Capon, and this uncoupling showed significantly anxiolytic effect in mice. In order to find lead compound with improved bioactivity, the present project will perform systematic structure-activity research on compound ZLc-002. Furthermore, we will design, synthesize, and evaluate the bioactivity of peptidomimetics based on the C-terminal two peptide A-V, four peptide E-I-A-V of Capon and the G-D/E-X-V ligand motif of nNOS PDZ domain to explore new series of compounds with anxiety effect, thus lay a solid foundation for the new anxiety drugs in possession of intellectual property.