Effect Of Hydrophobic Amino Acid Chain Spatial Structure On Amphiphilic Short Peptide Self-assembly

Self-assembly phenomena are ubiquitous in nature.It is the process from disorder to ordered structures of molecules.Self-assemblies occur at different scales,from molecules,particles,to even life tissues.Peptides have attracted many attentions and researche interests recently due to their excellent biocompatibility,ease of synthesis and modification.However,the self-assembly mechanism is still unclear,especially the role of amino acid side chain spatial structures.In this thesis,we have designed and synthesized two series of short peptides with the sequences of I_mL_nK（m,n=1-4）,short amphiphilic peptides composed of L type amino acids（^LI₃^LK）and D type amino acids(^DaI₃^DK)to explore the influence on the hydrophobic amino acid side chain spatial structure and different chiralities on peptide self-assembly.We hope that these works would unveil the meachnism of short peptide self-assembly.The main research works can be concluded as follows.（1）The effects of spatial structure of hydrophobic amino acid side chain on self-assembly have been studied using Ac-I₄K-NH₂ as the starting molecule.The isoleucine at different positions has been replaced by leucine one by one.The results showed that the side chains can affect the self-assembled nanostructures and secondary structures significantly.The morphologies of Ac-I₄K-NH₂ were dominated by nanofibers with only a few nanobelts.Nanotubes and nanofibers coexisted in Ac-LI₃K-NH₂ self-assemblies.Ac-ILI₂K-NH₂ formed uniform nanobelts.Ac-I₂LIK-NH₂ formed nanobelts and a few nanofibers.Ac-I₃LK-NH₂formed nanofibers and narrow nanobelts.CD results showed that secondary structurs of self-assemblies were variet with the Leu postion in the sequence.The difference of methylene position of in the side chain of Ile and Leu results in different lateral stacking abilities.The space steric hinderance between beta-sheet led to the morphogical difference of the nanostructures.（2）In order to further explore the space steric hinderance effects,two Leu residues were induced into the peptide sequences.AFM and TEM results showed that the morphology of the self-assemblies varied with the number and position of Leu residues.Ac-L₂I₂K-NH₂ self-assembled into helical nanofibers.Ac-IL₂IK-NH₂ formed nanobelts,and Ac-I₂L₂K-NH₂formed nanofibers.Comparing with the results of one Leu series,it was founded that peptides were apt to form wide nanobelts when Leu was located in the middle position,while nanofibers were formed at the N-terminal or near the Lys.It was indicated that Leu substitution could significantly affect the hydrogen bonds and the space steric hinderance,and thus affect the twisting degree of beta sheets.If space steric hinderance effects were enhanced,the hydrogen bonding effects would be reduced.（3）In order to investigate the chiral effect of the side chains of amino acid,we have studied to peptides,Ac-^LI₃^LK-NH₂ and Ac-^DaI₃^DK-NH₂.By mixing these two peptides at different molar ratios of 1:1,1:4 and 4:1.Their co-assembly properties were investigated.AFM results showed that Ac-^LI₃^LK-NH₂ formed left handed nanofibers while Ac-^DaI₃^DK-NH₂formed right handed nanofibers.In 1:1 mixing,right handed spiral nanofibers、left handed spiral nanofibers and no-spiral nanofibers coexisted.In 1:4 mixing,the morphologies were right handed nanofibers and no-nanofibers,and the right hand spiral nanofibers dominated.In4:1 mixing,left handed and no-spiral nanofibers coexisted.Combining the length proportion statistics and the results of molecular dynamics simulation and fluorescent spectroscopy,it was proved that the peptides partially co-assembled after mixing.