Investigations On The Self-assembly Behavior And Mechanism Of Ultrashort Bola Peptides

Peptides are a kind of small molecules between amino acids and proteins.By the collaboration of different non-covalent interactions,such as hydrogen bonding,hydrophobic,and aromatic interactions,peptides can self-assemble into different nanostructures,including nanofibers,nanoribbons,nanotubes as well as vesicles.As for the superior properties,such as good biocompatibility and abundant self-assembly morphologies,peptides self-assembly has become a new growth point in the biochemistry interdisciplinary,which is always regarded as important tool for the preparation of new materials with new functions.Amino acid is the basic unit of peptides,both the structure and the properties of amino acids have great impact on the aggregate morphologies and their corresponding structure.The researchers have done a series of work on peptides,different aggregates morphologies have been constructed and then realized their further application in different fields.As for the complexity of different non-covalent interactions,it is still quite different to control the aggregate growth along a certain direction.In fact,it is still quite difficult to construct a certain aggregate morphology and illuminate its formation mechanism by rational molecular design.Therefore,in this paper,we intend to design and synthesize series of short peptides and effectively control the shape of size of the assemblies by proper molecule design.Then,the formation mechanism of different assemblies will be illustrated.Based on the work carried out on KI₄K,we regulate the self-assembly behavior of different peptides by changing both the hydrophilic and hydrophobic amino acids of the peptides.Our results showed that,the aggregate morphology can be successfully controlled along a certain direction by proper molecule design.The contents mainly consisted of three parts:?1?In this work,we replace the two hydrophilic Lys?K?residues with two arginine?R?or histidine?H?residues to get two new cationic amphiphilic peptides,i.e.,RI₄R and HI₄H,respectively.The research shows that nanotubes and helical nanoribbons for KI₄K,flat and multilayered nanoribbons for HI₄H,and twisted and bilayered nanoribbons for RI₄R.These different 1D morphologies can be explained by hydration ability of different hydrophilic amino acid residues.The work clearly demonstrates the significance of hydrophilic amino acids in tuning self-assembled peptide nanostructures by influencing the lateral association and the z-direction?height?of?-sheets.?2?Peptide side chain residues have a very important influence on the morphology and size of the assembly.In this work about KI₄K,we design two series of bolaform peptides,with Set I consisting of KI₄K,KI₃NleK,KI₃LK,and KI₃TleK and Set II consisting of KI₃VK,KI₂V₂K,KIV₃K,and KV₄K.In Set I,substitution for the hydrophobic amino acid Ile in the C terminal altered its side chain branching but the hydrophobicity was retained.In Set II,the substitution of Val for Ile led to the decrease of hydrophobicity but the side chain?-branching was retained.Expect for KI₃TleK and KV₄K,the peptides can form nanotube.KI₃LK and KI₃NleK show smaller size,which means?-C shows promoting effect to lateral stacking of?-sheet.Maintaining the side chain?-branching mode of the core hydrophobic residues,the reduction in hydrophobicity is demonstrated to decrease the tube diameters for KI₃VK,KI₂V₂K,and KIV₃K.?3?Based on the research of Ac-KI₄K-NH₂,Fmoc-KI₄K-COOH,Ac-KI₄K-COOH,NH₂-KI₄K-COOH was designed to investigate the capping effect on peptide assembly.Ac-KI₄K-COOH can form a wider double belt while Fmoc-KI₄K-COOH forming fine fiber bundle and monolayer nanotubes for Ac-KI₄K-NH₂.Unfortunately,NH₂-KI₄K-COOH displayed little aggregating ability due to stronger hydrophilicity.In conclusion,the?-sheet monolayer will associate with the other along the height direction due to the hydrogen bonding interactions resulting from the uncapping–COOH.The steric hindrance interactions of the Fmoc-terminal prevent the lateral association of the elementary sheets but can lead to formation of nanofiber bundles.Thus,it's useful to change the terminal non-covalent bond force to control the assembly behavior in size and structure.