Study On Self-Assembly Of Photo-Responsive Antimicrobial Peptides And Their Antibacterial Properties

Antimicrobial peptides,as biomaterials against multi-drug resistant bacteria,have turned into the most promising antibiotic alternatives in dealing with infectious diseases by pathogenic bacteria.Compared with free antimicrobial peptides,the self-assembled antimicrobial peptides exhibit better biological effects.In addition,if the antimicrobial activity of antimicrobial peptides can be manipulated,the problem of persistent accumulation of drugs in the environment will be solved,which is of great significance for addressing bacterial drug resistance.Therefore,in this study,a series of photo-responsive antimicrobial peptides with different structural characteristics(symmetry,amino acid type,etc.)were designed,and the self-assembly behavior and antimicrobial activity under UV/visible light were further investigated to establish the relationship between the aggregate structure and antimicrobial properties.The main conclusions are listed as follows.1.A photo-responsive antimicrobial peptide amphiphile(NA)with symmetric structure was designed.The NA molecule has three arginines as the symmetric center,and two ends of p-butyl azobenzene as the hydrophobic part,where alanine connects arginine and azobenzene.The results showed that the assembly of NA molecules grew from vesicles to short rod-like structures,and finally formed fibrous network structure,revealing the behavior of aggregate growth.The NA molecules showed broad-spectrum antibacterial effects against Gram-positive bacteria(S.aureus),Gram-negative bacteria(E.coli,P.aeruginosa)and fungi(C.albicans).Also,NA molecules have good inhibitory and scavenging ability activity on the biofilm activity formed by P.aeruginosa.Through the study of its antibacterial mechanism,it was found that the fibrous network structure assembled by NA possess abundant positive charge,which can tightly wrap the bacteria by electrostatic interaction,leading to the death of bacteria.The NA molecules have good photo-responsiveness.Upon UV light illumination,the trans-cis isomerization of azobenzene(Azo)molecules occurred,and NA molecules no longer showed the characteristics of aggregate growth,but change from network structure to smaller vesicles and some short rod structures.As the charge is not as rich as network structure,antibacterial activity was decreased.2.Photo-responsive antimicrobial peptide amphiphile(C4A3R3,C4A3K3 and C4A3H3)containing different amino acids were designed.The hydrophobic parts of the antimicrobial peptides are p-butyl azobenzene,carrying three positively charged amino acids(arginine R,lysine K and histidine H).C4A3R3,C4A3K3 and C4A3H3 all formed fibrousnetwork structure at high concentration,while only C4A3H3 assembled to vesicles at low concentration,and the other two coexisted vesicle and fibrous network structure.By comparing the antibacterial activities,it was found that C4A3R3 had excellent broadspectrum antibacterial activity,and had good inhibition and scavenging ability on the biofilm formed by P.aeruginosa,followed by C4A3K3,while C4A3H3 showed no obvious antibacterial activity.The excellent antimicrobial activity of C4A3R3 is due to the network structure that not only binds bacteria firmly by electrostatic interaction,but also partially inserts into the bacterial outer membrane,resulting in bacterial death.After UV light irradiation,the assembly changed into smaller vesicles or short rod-like structures due to trans-cis isomerism of Azo groups,and the transformation of assembly morphology resulted in weaker interactions with bacteria,causing a drop in antibacterial activities.