Regulation Of The Morphologies Of Aggregates Self-Assembled Or Co-Assembled From Bola-Type Ultrashort Peptides And Their Formation Mechanism

Molecular self-assembly is a process in which molecules form ordered aggregates"Bottom-Up"approach and driven by various non-covalent interactions.It is always regarded as important means for synthesizing new materials and generating new functions.Among all the building blocks,peptides have attracted intense attention in the field of molecular self-assembly due to their diversisty,easy synthesis and modify,easy degradation,and low-toxicity advantages.Through self-assembly,peptides can form various nanostructures,such as micelles,vesicles,nanorods,nanofibers,nanoribbons,and nanotubes,and then show wide applications in photoelectric catalysis,biosensing,tissue culture,drug delivery,anti-cancer,anti-tumor,etc.However,the nature and morphology of a single peptide self-assembled in water to form an assembly often cannot meet actual needs.Therefore,how to expand the ways to regulate the morphology of peptide assemblies and construct peptide assemblies with different morphologies on the basis of existing research work is still a difficult problem in the field of peptide self-assembly.Based on this,this article design and synthesize a series of Bola-type ultrashort peptides based on our previous work,and regulate the morphology and size of the assembly through reasonable molecular design,introduction of organic solvents and the co-assembly approach,in order to construct different morphologies.Different assemblies provide new ideas.The research mainly focused on two aspects:On the one hand,by changing the type of solvent,the regulation of the morphology and size of the peptide assembly was realized by means of by changing the solvent;on the other hand,the binary system of the peptide was constructed through co-assembly,in which the aggregates morphology was modulated by adjusting the degree of torsion.Effective control of the morphology of the assembly.The specific research content is as follows:（1）Based on the molecular sequence of Ac-KI₄K-NH₂,the hydrophilic amino acids Lys at both ends were replaced with His and Arg,and Ac-RI₄R-NH₂and Ac-HI₄H-NH₂were designed and synthesized.At the same time,the solvent was replaced from water to methanol,and the self-assembly behavior of the above three peptides in methanol was investigated in details.The results demonstrated that,the width of the assembled nanostructures of the three peptides in methanol is reduced as a comparison to those formed in water,narrower nanofibers,helical ribbons and multi-layer flat ribbons are their dominant nanostructures,respectively.This is mainly due to the influence of the introduction of methanol on the hydrogen bonding and hydrophobic interaction during peptide assembly.At the same time,the assembly morphology of the three peptides in methanol is also significantly different,which is mainly caused by the different ability of them to form hydrogen bonds with methanol.The above results indicated that by proper design of peptide molecular structure and the change of the solvent environment,the morphology and size of the assemblies can be regulated properly.（2）By changing the hydrophilic amino acid residues of Ac-KI₄K-NH₂,two asymmetric short peptides,Ac-HI₄K-NH₂and Ac-KI₄H-NH₂were designed and synthesized,their self-assembly and co-assembly behaviors were investigated in systemically.By changing the mixing ratio,the co-assembly behavior of the two peptides was investigated in details.The results demonstrated that thetwo peptides,Ac-HI₄K-NH₂and Ac-KI₄H-NH₂can self-assemble to form flat ribbons and twisted ribbons,respectively.Buta completely different assembly morphology can be obtained by their cosembly process.The morphologies of the co-assemblies are closedly related to the mixing ratio of the two peptides.When the molar ratio of Ac-HI₄K-NH₂and Ac-KI₄H-NH₂is 1:5,the dominant assembly morphology is twist ribbons,twist ribbons and nanotubes are formed at 1:1 molar ratio,and nanotubes are formed at 5:1 molar ratio.Such results indicated that the morphology of the assembly can be effectively regulated by changing the terminal groups,and the aggregates morphologies can be changed by changing the relative ratio of the two peptides through changing the torsion of the sheet.The above work provides new approach for the construction of nanotubes.（3）Two short peptide molecules Ac-RI₄H-NH₂and Ac-HI₄R-NH₂were designed and synthesized,and their self-assembly and co-assembly behaviors were systematically investigated.The results domonstrated that Ac-RI₄H-NH₂and Ac-HI₄R-NH₂self-assemble to form flat ribbons and twisted ribbons,respectively.Then,the coassembly of peptides was investigated by mixing them at different molar ratios.When Ac-RI₄H-NH₂and Ac-HI₄R-NH₂are at the ratio of1:5,1:1 and 5:1 twisted ribbons,nanotubes and twisted ribbons can be formed respectively.This vertifies again that the aggregate morphology of the aggregates can be regulated by changing the mixing ratio through torsion modulation.Such a work provides effective methods for nanotube fabrication.