Investigations On The Aggregates Self-assembled From Bola Peptides And Their Self-assembly Dynamic Process

Peptides are a kind of small molecules between amino acids and proteins.Because of their good biocompatibility,easy synthesis and modification,etc.,they have attracted extensive attention and in-depth research in the fields of chemistry,biology,and materials science.Peptide self-assembly refers to the process in which peptide molecules spontaneously form an ordered assembly from bottom to top under the cooperative action of various non-covalent bond forces.Self-assembly of peptides can form assemblies with rich morphology,and these assemblies can be applied in different fields.In peptide self-assembly,although the existence of different weak interaction forces has been proven,their synergistic effect is still unclear.The directional control of the morphology and size of the polypeptide assembly is still a difficult problem in the field of peptide self-assembly.Based on this,we designed and synthesized a series of ultrashort peptides on the basis of the previous research work,adjusted the morphology of the assembly by reasonably changing the molecular structure and solvent composition,and investigated its self-assembly behavior and the dynamic process of assembly formation in detail.The research content mainly includes the following three aspects:（1）Based on the previous research work of Ac-KI₃-CONH₂（KI₃）,this thesis designed and synthesized Ac-KIIV-CONH₂（KIIV）,Ac-KIVI-CONH₂（KIVI）and Ac-KVII-CONH₂（KVII）.The Bola-like peptides were constructed through hydrogen bonds between the end groups,and the effect of the sequence of amino acid residues on the self-assembly behavior of the Bola-like peptide was investigated.The study found that KIIV self-assembled to form double-layer nanotubes with a diameter of 7-9 nm.The KVII assembly size increased significantly,forming double-layer nanotubes of diameter 23-25 nm.KIIV and KVII form double-layer nanotubes mainly because they can form a Bola-like structure through hydrogen bonds between the end groups during assembly,showing similar assembly characteristics to Bola-like peptides.In this process,due to the change of the position of valine V,the effect ofβ-C is changed.In the Bola-like molecule formed by KIIV,theβ-C of V is wrapped by the I residue,which limits its promotion of sheet lateral stacking.The ability to form nanotubes results in a smaller diameter of nanotubes.Conversely,when V is closer to K,KVII has a larger diameter to form nanotubes.On this basis,we investigated the dynamic process of the formation of KVII nanotubes and found that the formation of nanotubes went through a process from fiber to twisted ribbon,then to helical ribbon,and finally assembled to form a tube.The above research provides new ideas for the construction and size control of nanotubes.（2）By changing the position of valine V in the Bola peptide molecule,Ac-KI₃VK-CONH₂（KI₃VK）,Ac-KI₂VIK-CONH₂（KI₂VIK）,Ac-KIVI₂K-CONH₂（KIVI₂K）and Ac-KI₃VK-CONH₂（KI₃VK）,Ac-KI₂VIK-CONH₂（KI₂VIK）,Ac-KIVI₂K-CONH₂（KIVI₂K）and Ac-KVI₃K-CONH₂（KVI₃K）were designed and synthesized,to explore the influence of the sequence of amino acids on the morphology of the assembly.It is found that KI₃VK and KI₂VIK can self-assemble to form a nanotube structure,while KIVI₂K and KVI₃K self-assemble to form a double-layer twisted ribbon and helical ribbon structure,respectively.The main reason for the above results is that the change of the position of valine V makes the steric hindrance of isoleucine I in the hydrophobic region of the peptide molecule change,which leads to the assembly of the peptide to form nanotube structures with different diameters.The above studies have shown that by rationally adjusting the sequence of amino acids in the peptide,the morphology of the assembly formed by the polypeptide can be effectively adjusted.（3）The self-assembly behavior of the peptide Fmoc-KI₄K-CONH₂ was regulated by introducing the organic solvent hexafluoroisopropanol（HFIP）into the system.Studies have shown that Fmoc-KI₄K-CONH₂ self-assembles to form fiber bundles in pure water.When a small amount of HFIP is introduced into the system,the morphology of the assembly changes from fiber bundles to thin nanotube structures.This is because HFIP and the aromatic ring on the Fmoc group produce an interaction force,which reduces theπ-πstacking effect and changes the morphology of the assembly.Continue to increase the HFIP content can effectively reduce the hydrophobic effect,resulting in the formation of finer nanofibers.This indicates that different assembly morphologies can be formed by changing the composition of the peptide solvent,which provides a new idea for the construction of new nanomaterials.