The Assembly Of Amphiphilic Oligopeptide Derivatives And The Study Of Antibacterial Performance

During the long history of mankind,microbial infection has always been a major problem that invaded human health,and even caused serious harm to human life.Therefore,it is of great significance to develop materials with good antibacterial functions.Compared with traditional antibacterial materials,peptide-based nanoparticles presented prominent advantages due to their good biocompatibility and biodegradability.More importantly,peptides have good flexibility in design.Therefore,peptide-based antibacterial materials have received widespread attention.More and more studies have shown that antimicrobial peptides(AMPs)have broad-spectrum antibacterial activity.Due to their unique membrane activity bactericidal mechanism,the use of antimicrobial peptides is not susceptible to the incasion of identification problems.Here,we will focus on the design and antibacterial properties of amphiphilic oligopeptides and derivatives.By exploring the sequence structure,modification strategies,assembly behaviors of functional peptides on their antibacterial properties,we will discess the machanism,which can provide new ideas for the preparation of safer and more effective antibacterial materials.In the first chapter,the charateristics of bacterial infection and the harm to human health are briefly described.Among them,the advantages and disadvantages of antimicrobial peptides as a safe and effective antimicrobial material are emphasized.Based on these,the background of this study is discussed.In chapter 2,we have designed and synthesized an acidity-triggered amphiphilic oligopeptide(OPA)for antibacterial treatment based in the unique slightly acidic environment of the microbial infection site.As an effective antibacterial agent,C₁₆-A₃K₄-CONH₂ is none-selective membrane destructive due to its large amount of positive charge.It will be toxic to normal human cells during the circulation in the body.In order to overcome this shortcoming,we will change the nature of its charge,amidate the side groups of lysine,and react with 2,3-dimethylmaleic anhydride(DMA)to form C₁₆-AAAK(DMA)K(DMA)K(DMA)K(DMA)-CONH₂,the generated OPA self-assembles to form negatively charged spherical nanoparticles,and its toxicity will also be greatly reduced.After entering the microbial infection site,the acid-sensitive?-carboxamide is hydrolyzed to expose the positively charged C₁₆-A₃K₄-CONH₂.At the same time,the cationic antimicrobial peptide self-assembles into rod-shaped nanofibers,and the microbial membrane of pathogenic bacteria interaction,causing it to rupture and cause the death of microorganism.Relevant experimental results show that this kind of amphiphilic oligopeptide,which is a combination of acidity triggering charge reversal and morphological transformation,has a good inhibititory effect on Saccharomyces cerevisiae,Escherichia coli and Staphylococcus aureus.In chapter 3,in this part,we propose the concept of combining reactive oxygen free radicals(ROS)and amphiphilic oligopeptides to improve the therapeutic effect.Through the research on the bactericidal mechanism of the oligopeptides in the previous chapter,we will retain the normal properties of the oligopeptides and the?-helical secondary structure.On this basis,we have unsaturation on the hydrophobic tail of the amphiphilic oligopeptide.The double bond of linoleic acid forms a derivative(LA-KLAKKLAK-CONH₂).This material can generate the corresponding hydroperoxide(LAOOH-KLAKKLAK-CONH₂)under the oxidation of a small amount of oxidase(Lox).Active oxygen free radicals(ROS)are generated under the catalysis of iron ions(Fe²⁺).ROS,as another effective bactericidal mechanism,plays a synergistic therapeutic effect with oligopeptides.The research results show that by dating unsaturated fragments,the material can produce reactive oxygen free radicals(ROS)under the catalysis of Fe²⁺.The two mechanisms are combined treatment,which is resistant to Staphylococcus aureus,Escherichia coli and methicillin-resistant golden yellow Staphylococcus and other bacterial species have more significant therapeutic effects.