胱氨酸打结肽具有多种多样的生物活性以及卓越的酶稳定性，使其成为了国内外各大药物公司竞相追逐研究的潜在药物和诊断试剂。然而目前仍缺乏有效的方法来快速获得胱氨酸打结肽及其衍生物三维结构，为设计活性更高的分子提供结构基础。本课题提出使用准外消旋结晶法来稳健、快速获得胱氨酸打结肽及其衍生物的三维结构新策略，并结合分子对接技术分析胱氨酸打结肽结构改变对于活性影响机制，来加快胱氨酸打结肽药物结构活性关系研究，缩短胱氨酸打结肽新药的研制过程。通过对胰蛋白酶抑制剂MCoTI-II及其衍生物进行准外消旋结晶研究，将证实新策略的稳健、快速性。其次，分子对接技术对于复合物结构的构建将揭示MCoTI-II结构改变对于其活性影响的机制。最后，利用准外消旋结晶技术对氯毒素三维结构的确定，将为今后氯毒素结构功能关系以及功能机制的研究提供可靠的结构数据。

Cystine knot peptides, with a wide variety of biological activity and superior enzyme stability, are promising agents for diagnostic and therapeutic applications, as widely described by pharmaceutical company. However, there are still no effective way to quickly obtain three-dimensional structure of cystine knot peptides and its derivatives to provide the structural basis for the design of more active molecules. Here, we propose a new strategy that the three-dimensional structure of cystine knot peptides and its derivatives can be quickly obtained by using quasi racemate crystallization. Combined with molecular docking technology, we will reveal the influence of structure on the activity, which promotes the study of structure-acivity relationship, thus shortening the development process of cystine knot peptides drugs. The robustness and rapidity of this strategy will be demonstrated by quasi-racemic crystallization of MCoTI-II and its derivatives. Secondly, the crystal structure of MCoTI-II complex, obtained from molecular docking techniques, will suggest the influence of structural changes on activity. Moreover, the study of structure of chlorotoxin by quasi-racemic crystallization three-dimensional, will provide a reliable structure for future studies of the structure-acivity relationship of chlorotoxin and functional mechanism.