Construction Of Peptide Trimer Based On Dynamic Disulfide Bond And Acylhvdrazone Bond

Dynamic covalent bond is a reversible covalent bond that can exist stably like a covalent bond,and can dissociate like a non-covalent bond.It can be reversibly broken and formed under appropriate conditions,and there are few side reactions in this process,which makes it widely used.Disulfide bond and acylhydrazone bond are the most widely used dynamic covalent bonds,and both are sensitive to the pH of the solution.By changing the pH value of the solution,the exchange reaction between the disulfide bond and the acylhydrazone bond can be selectively activated or stopped.A suitable pH range can be determined so that the disulfide bond and the acylhydrazone bond exist stably at the same time.As a special linker,dynamic covalent bonds are currently being introduced into the fields of short peptide self-assembly and peptide drug cyclization.Short peptide molecules with few amino acids have a clear structural composition,and the synthesis of short peptide molecules is relatively simple and easy to be modified.Therefore,the self-assembly of short peptide molecules has received widespread attention.It is one of the research hotspots in the field of molecular self-assembly.We proposed a new method to promote the self-assembly of peptides to form peptide trimer by introducing disulfide bond and acylhydrazone bond into peptides at the same time.Meanwhile,the property of orthogonal pairing between cysteine(Cys)and penicillamine(Pen)was used to specifically generate peptide trimer.Finally,this method was applied to the self-assembly process of some biologically active peptide trimer.There are three chapters included:Chapter 1:Firstly,we introduced the development and properties of dynamic covalent bonds and several common dynamic covalent bonds.Secondly,the characteristics of peptide self-assembly and the application of peptide self-assembly materials were introduced.Then,the self-assembly process of two types of biologically active peptide trimer was introduced:the self-assembly of the protein molecule coiled coil structure and the collagen triple-helix structure.Finally,based on the related research background,the research ideas and significance of this paper were put forward.Chapter 2:We designed and synthesized some model peptides.Then,we modified the model peptides to form disulfide bond and acylhydrazone bond.We promoted the self-assembly of model short peptides to form peptide trimer through the synergy of the two dynamic covalent bonds.At the same time,cysteine(cys)and penicillamine(pen)were introduced into the reaction system.Through the orthogonal pairing of cys-pen,model short peptides produced only one peptide trimer.Chapter 3:Based on the results of experiments in Chapter 2,we used this method to construct the short sequence protein molecule coiled coil trimer and collagen peptide trimer.In the end,we summarized and prospected the work of this thesis.