Desin,Synthesis And Activity Research Of Novel Analogues Of Short Cationic Antimicrobial Peptides

The abusing of antibiotics leads to the emergence of resistant bacteria.So it is particularly significant to develop novel antibiotics.Antimicrobial peptides(AMPs),or host defense peptides are important components of innate immune systems,show promise as therapeutic agents against a broad spectrum of microbes including bacteria,fungi and viruses.But there are still some challenges to their applications,such as potential toxicity to humans,sensitivity to harsh environmental conditions,lack of selectivity against specific strains and high production costs.In order to improve the clinical use of AMPs,researchers have devoted to the following aspects:improving peptide stability,reducing toxicity,enhancing the antimicrobial activity and saving the production cost of AMPs.Anoplin was modified with D-amino acide and NLS was modified with acridine.Through the antibacterial activity and mechanism research of the analogues,we have found that anoplin-4 displayed the highest antimicrobial activity among the Anoplin analogues.And anoplin-4 showed low toxicity to host cells,indicating high bacterial selectivity.Furthermore,the mortality rate of mice infected with Escherichia coli was significantly reduced by anoplin-4 treatment relative to anoplin.Besides,in the research of NLS analogues,both analogues displayed significant antimicrobial activity against Gram-negative bacteria and-positive bacteria compared to NLS and 9-Chloroacridine.And the antimicrobial activity of dimeric(Acr3-NLS)2 was significantly higher than that of Acr3-NLS.And then through the action mechanism research,we found that both analogues could kill bacteria through double action mechanism.The action target of Acr3-NLS and(Acr3-NLS)2 is not only the bacterial membrane but also the intracellular DNA according to our experimental results.In conclusion,we have systhesized two analogues with good antibacterial activity Anoplin-4 and(Acr3-NLS)2.Those two analogues were thought to be potent agents for infection treatment,and new lead compounds might be developed with these methods.