细胞膜磷脂酰丝氨酸PS与许多重要疾病密切相关，膜联蛋白Anx成员与细胞膜磷脂酰丝氨酸PS结合，具有良好的药物发现价值和新药研发前景。人类Anx家族成员及其剪切体多达19个，其生物学功能尚不清楚。. 本项目拟系统性地深入剖析人Anx家族各成员的结构与其进化和功能的关系；从中筛选并发现以PS为靶点的、具有较好药效学作用和低毒副作用的Anx类候选药物；将揭示人Anx蛋白质结构与其药效、毒副作用的关系及其机制，在此基础上通过结构优化和蛋白质工程改造，研制以磷脂酰丝氨酸为靶点，性能更好、安全性更佳的原创生物药物。本课题组长期从事Anx家族（尤其是AnxV）的结构与功能关系及其创新药物研究，前期已经围绕AnxV结构与功能及毒性的关系，发表研究论文34篇，含SCI论文16篇，已获AnxV相关中、美、欧盟发明专利7件，申请发明专利5件，2个AnxV衍生创新生物药物已经转让企业，并已完成临床前研究。

Membrane phosphatidylserine (PS) is tightly associated with many diseases. Members of Annexin family have the phospholipid-binding ability, displaying promising potential for drug discovery and development. There are 19 members or splicing alternatives in human annexin family, their functions still remain unclear. This proposal aims to systematically investigate the relationship between the structure and evolution, function of each individual member of human annexin family, and to screen and discover biologic candidates with well efficacy and less toxic effect, by targeting at phosphatidylserine. . This proposal will reveal the relationship between the protein structure and efficacy, toxicity of annexin family members and the underlying mechanisms. Based on the analyses and knowledge obtained from the above studies and relied on the approaches of structural optimization, molecular design and protein engineering, this proposal aims to develop innovative biopharmaceutical, targeting phosphatidylserine, with higher biological activities and efficacy, and better safety. . The present research team has been long-timely devoted to the structural and functional relationship study of Annexin family, mainly focused on annexin V, and the development of innovative new drug from annexins. We have already published 34 research articles, among which 16 papers appeared in SCI journals, produced from our previous studies on the structure-function-toxicity relationship of annexin V.. From the studies on annexin V, we have gotten 7 patent authorizations from China, American and Europe. 5 patent applications under review. Two innovative biopharmaceuticals derived from annexin V have finished all the preclinical studies and ready for clinic trail application.