Synthesis And Rapid Structure Determination Of Polydisulfide Bond-Containing Peptide Drugs

Objective Through the synthesis of L-type and D-type polydisulfide bond-containing peptide PnIA(A10L)and its analogues by chemical synthesis,and then the crystal structure of polydisulfide bond-containing peptide PnIA(A10L)was obtained by quasi racemic crystallization technology,which laid a foundation for further research on the structure activity relationship of polydisulfide bond-containing peptide.Method Firstly,the aim of this paper is to develop a synthesis method of polydisulfide bond-containing difficult peptide represented by PnIA(A10L),so as to complete the synthesis of polydisulfide bond-containing peptide PnIA(A10L)and its diaminodiacid analogues,and purify them later to obtain pure products,which provide raw materials for the subsequent quasi racemic crystallization.Then,the crystal structure of PnIA(A10L)was obtained by using the developed quasi racemic crystallization technology for L-D co crystallization.Results We have successfully developed the synthesis method of polydisulfide bond-containing difficult peptide represented by PnIA(A10L),and successfully synthesized PnIA(A10L)and its diaminodiacid analogues,and obtained the crystal data of PnIA(A10L)by quasi racemic crystallization.Conclusions We have successfully developed the synthesis method of polydisulfide bond-containing difficult peptide represented by PnIA(A10L),and successfully synthesized PnIA(A10L)and its diaminodiacid analogues,which provides a new idea for the future research of polydisulfide bond-containing peptide.The crystal data of PnIA(A10L)were obtained by quasi racemic crystallization,which verified that the quasi racemic crystallization can be robust and fast to obtain the crystal structure of polydisulfide bond-containing peptide and provide important structural data for the future research on the structure and the relationship between structure and activity of polydisulfide bond-containing peptide.