The Effect Of Aromatic Group On Peptide Self-Assembly

Peptides can self-assemble into distinct supramolecular nanostructures that have potential applications in biomedicine,material science,and tissue engineering.The self-assembly is driven by cooperatice interaction of various noncovalent forces.Aromatic???interaction is a directional force that can regulate the peptide self-assembly.Initiated from our previous study on Nap-FFGPLGLARK-NH₂,the present research investigated the effect of aromatic groups on the peptide self-assembly by changing the aromatic capping group,simplifying the molecular structure,altering the amino acid type of the motif,adjusting pH/ionic strength of the solution and loading the Nile Red dye experiment.Firstly,a series of molecules based on our previous experiment,X-FFGPLGLARK-NH₂?X=Fmoc,Nap,Ac?were designed to study the effect of aromatic capping group on the self-assembly behavior.The results showed that the aromatic capping group could influence the self-assembled structure to a large extent.Fmoc-FFGPLGLARK-NH₂ could self-assemble into the dense fibers at low concentrations and load more Nile Red dye molecules.However,Nap-FFGPLGLARK-NH₂ and Ac-FFGPLGLARK-NH₂ could self-assemble at high concentrations and load less Nile Red dye molecules.Besides,When the pH of the solution increased,the fibers tended to be aggregated due to screening of the surface charge.A large number of aromatic rings distributed on the surface of the fibers.The specific orientation of?-?interaction regulated the growth direction of the fibers drived them to pack laterally to form the fibril bundles.Secondly,in order to exclude interference from other types of amino acid,another series of peptides,X-FFGK-NH₂?X=Fmoc,Nap,Ac?were designed to simplify the molecular structure.The self-assembly behaviors showed that Fmoc-FFGK-NH₂ could self-assemble into the dense fibers and load more Nile Red dye molecules due to more aromatic groups.Nap-FFGK-NH₂ and Ac-FFGK-NH₂ could self-assemble at high concentrations and load less Nile Red dye molecules due to less aromatic groups.the pH increase and the NaCl addition could screen the surface charge and thereby promote the molecular aggregation.In this case,the electrostatic repulsion was weakened and the?-?stacking of the aromatic rings became dominant to determine the self-assembled structures.The molecules formed a twisted supercoiled assembly driven by the specific orientation force.The supercoiled nanostructure formation was relatively stable when the charge changed.Finally,in order to investigate the effect of aromatic groups on the peptide self-assembly with different hydrophobic side chains,the peptides of Fmoc-XXGK-NH₂?X=Cha,F,I,G?with the same aromatic capping group and different hydrophobic residues were designed.The self-assembly behaviors showed that Fmoc-ChaCha-GK-NH₂ existed a greater torque due to the rigid cyclohexyl ring structure and the strong hydrophobicity of the Cha also made it easy to form more cavity structures for the assembly.Eventually,Fmoc-ChaCha-GK-NH₂ formed the supercoiled assembly under the cooperatice interaction of?-?interaction,hydrophobic interaction and electrostatic interaction.Relatively,Fmoc-FFGK-NH₂ formed the twisted fiber structure due to the weak hydrophobicity of the benzene ring and the absence of rigid cyclohexyl ring.However,Fmoc-IIGK-NH₂ and Fmoc-GGGK-NH₂ formed the relatively smooth fibrous structure eventually due to the weak???interaction and the primary fibrils.The Nile Red loading experiment found that the loading of Nile Red decreased gradually when the X of Fmoc-XXGK-NH₂ from Cha to F,I and G,which showed that the assembly capacity weakened gradually.Further,?cyclodextrin could destroy the structure of the supercoiled assembly by interacting with the hydrophobic cyclohexane rings,which promoted Fmoc-ChaCha-GK-NH₂ to release Nile Red compared with Fmoc-FFGK-NH₂ and Fmoc-IIGK-NH₂.