Construction Of Self-assembled Oligopeptide Nanomaterials And Their Biomedical Applications

In recent years,self-assembled oligopeptide nanomaterials have received much attention due to their emerging properties.Oligopeptide molecules can form soft materials such as nanospheres,nanofibers,and nanotubes through self-assembly,which have been widely used in biomedical and biotechnology fields such as cell culture,biological template,optics,drug delivery,biocatalysis,cancer treatment and antibiotics.Here,we have designed and prepared a series of functional oligopeptide molecules,and systematically studied their self-assembly mechanism and application in biomedicine.Based on extensive research in this field,the first chapter of the paper summarized the recent advances in oligopeptide self-assembly and its biomedical applications.First,based on the structure and properties of oligopeptide molecules,several typical amphiphilic oligopeptides were described.In addition,in order to provide insights into the assembly mechanism of self-assembled oligopeptide,the secondary conformation of the self-assemblies was reviewed.Finally,the application of self-assembled oligopeptide in biomedicine was summarized.In Chapter 2,a novel oligopeptide nanoprobe for targeted cancer cell imaging was successfully prepared.Based on solid phase peptide synthesis,a tryptophan-phenylalanine-phenylalanine-tryptophan?WFFW?tetrapeptidewas obtained,which generated photostable and tunable fluorescence emission signals from340 nm to 500 nm.The WFFW tetrapeptide could self-assemble into a spherical nanostructure with enhanced fluorescence intensity.Driven by?-?stacking and hydrogen bond interaction,WFFW co-assembled with arginine-glycine-aspartic acid?RGD?modified WFFW to form a cancer-targeted fluorescent nanoprobe,which could selectively image the cancer cells.In Chapter 3,a novel aligned nanofiber fluid was obtained from self-assembly of C₁₆-AAAAAKK-CONH₂?OPA1?oligopeptideamphiphile.Small-angleX-ray scattering?SAXS?indicated that the microscopic fibers were grouped by bundled nanofibers with average diameter of⁶.6 nm.Scanning electron microscopy?SEM?and SAXS revealed that the parallel arrangement of nanofibers could be immediately enhanced by thermal pathway.The well-ordered alignment of nanofiber fluid after heating was further uncovered by²H NMR spectrum,with a residual quadrupolar coupling?RQC?splitting of ca.52 Hz at 10 wt%.Originating from the excellent alignment and good mobility,self-assembled fluid achieved the precise acquisition of residual dipolar couplings?RDCs?of biomolecules,such as proline and raffinose.In a proline model,a very low quality factor?Q factor?value of 0.057 was obtained via the linear fitting.Thus,the aligned nanofiber fluid provided a great potential for structural elucidation of molecules through RDCs measurement.Because many biomolecules can just be completely dissolved in organic solvents,constructing organic solvent-based aligned media is very pursued.Therefore,a novel DMSO-bearing aligned medium from self-assembled oligopeptide amphiphile was successfully prepared for elucidating biomolecule structures in the Chapter 4.In detail,a flexible C₁₆-AAAAAKEE-CONH₂?OPA2?oligopeptide amphiphile was prepared,which engaged in molecular self-assembly in DMSO and yields ordered nanowire matrix due to the hydrogen bonding and van der Waals interactions.SAXS indicated that the microscopic nanowires were grouped by bundled fibers with average diameter of⁶.2 nm.The microscopic order combining with good mobility allowed the oligopeptide lyotropic liquid crystal as a suitable aligned medium to measure the residual dipolar couplings for structural determination of biomolecules in DMSO-d6basedNMR,suchasEstrone,Artemisininand10-Hydroxycamptothecine.