Research On The Affecting Factors Of The Antimicrobial Rate Of Amphiphilic α-Helical Antimicrobial Peptides

Among the top ten causes of death in the world,respiratory infections rank third,among which bacterial infections such as drug-resistant Staphylococcus aureus,Mycobacterium tuberculosis,and Acinetobacter baumannii are the main causes of death.At present,the world is facing bottlenecks in the field of antibiotic research and development,such as huge investment,slow development,and no major breakthrough in the sterilization mechanism.At the same time,the mortality rate of bacterial infectious diseases is also increasing.With the abuse of antibiotics,more and more super-resistant bacteria have appeared,and their drug resistance is getting faster and faster.Therefore,in terms of the current situation,humans urgently need to discover new antibacterial agents and new treatment methods.In recent years,people have discovered a new type of antibacterial active substanceantibacterial peptides(AMPs).Antibacterial peptides are endogenous peptides encoded by genes and synthesized by ribosomes.They are widely distributed in various organisms in nature and resist external microorganisms.It plays an important role in the invasion process,so antimicrobial peptides are regarded as one of the potential antibiotic alternatives for the treatment of drug-resistant bacterial infections.Fast and efficient bactericidal action is one of the important characteristics of antimicrobial peptides over conventional antibiotics,which is also one of the main reasons why antimicrobial peptides are not easy to cause microbial resistance.However,the structural parameters and potential mechanisms that affect the sterilization speed of antimicrobial peptides are still unknown.In this project,we used the natural amphiphilic α-helical antimicrobial peptides AsCATH4 and As-CATH5 previously discovered in the Chinese alligator by the research team as templates to design a series of peptide modifications and conduct a wide range of structure-activity relationships.(SAR)Research.The results show that hydrophobicity is a key structural parameter that determines the sterilization speed of amphiphilic α-helical antimicrobial peptides.At the same time,antimicrobial peptides with higher hydrophobicity exhibit a faster sterilization speed.Mechanism studies have shown that with the increase in hydrophobicity,the speed of α-helical antimicrobial peptides binding to bacteria,the speed of neutralizing endotoxin(LPS),the speed of penetrating the outer membrane of bacterial cells,and the speed of penetrating the inner membrane of bacterial cells The speed will gradually increase.Compared with antimicrobial peptides with lower hydrophobicity,antimicrobial peptides with higher hydrophobicity can be inserted deeper into the bacterial cell membrane,thereby inducing membrane permeation and cell death more rapidly.In addition,antimicrobial peptides with high hydrophobicity are not easy to cause bacteria to develop drug resistance due to their fast sterilization speed.At the same time,antimicrobial peptides with high hydrophobicity also show a faster sterilization speed in vivo in the mouse skin wound infection model.Better treatment of bacterial infections.The results of this research show that the hydrophobicity of antimicrobial peptides plays an important role in improving the sterilization speed of amphiphilic α-helical antimicrobial peptides and optimizing the treatment effect.It also shows that the sterilization speed is an important physical and chemical property of antimicrobial peptides.The design and structural optimization of antimicrobial peptide-related drugs require great attention.