本项目拟发展高效合成不同类型二氨基二酸的新方法，并将其作为二硫键替代工具用于合成多肽药物，进而研究二硫键化学替代类多肽药物的结构-活性关系。具体课题设计及拟实现的目标主要包括：⑴ 高效合成含有不同正交保护基及新结构的二氨基二酸，使其可以便捷的用于含有多对二硫键多肽分子的合成；⑵ 合成新型基于巯基的二氨基二酸并将其用于多肽药物的合成；⑶ 将不同类型的二氨基二酸用于含有不同二硫键数目及位置的多肽药物的合成。测试通过不同二氨基二酸替代后的多肽药物的结构、活性变化，并结合理论化学计算的方法研究结构-活性关系，归纳二硫键化学替代类多肽药物的构效关系规律，建立具有普适性的多肽药物中二硫键替代策略。依据该规律合成重要的多肽药物，以期获得结构、活性俱佳的多肽分子。

In the proposed project, we plan to develop new strategy for the synthesis of diaminodiacids with different types.The diaminodiacid should be act as a linkage to replace the disulfide bond and then studied the structure-activity relationship of peptide drug analogues. We design to realize the objective including follow three part: (1) firstly, develop new method to increase the efficiency of the synthesis of diaminodiacid with different orthogonally protective groups or new structures, these compounds can be used in the synthesis of peptide with one or more disulfides conveniently; (2) secondly, develop new diaminodiacid that contain thiol, we plan to use the new thiol-diaminodiacid to synthetise peptide drugs; (3) finally, we use different types of diaminodiacids to syntheties peptide drugs with different disulfide numbers and replace the disulfide bonds in different positions. We plan to study the structure-activity relationship through compare the structure and bioactivity of peptide drugs that with different disulfide replaced types, and then established a universal disulfide bond replaced strategy. Ultimately, we can syntheties peptide drug analogues with good bioactivity according to the new strategy.