Design, Synthesis And Biological Activity Of Novel Antimicrobial Peptides Of Natural Antimicrobial Peptides MPI And Anoplin

Although it has been found that a large number of natural antimicrobial peptides are expected to replace the abuse of traditional antibiotics, but natural antimicrobial peptides itself exist many drawbacks and limit its application as a clinical drug, especially in the toxicity and proteolytic digestion aspect. Many new chemical methods are applied to the study of the structural modification of natural antimicrobial peptides, in order to improve its shortcomings. Click Chemistry as a more secure, efficient and convenient method has been applied to a number of areas, and the use of it on the structural modification of the natural antimicrobial peptides rarely reported. This subject on the basis of previous studies, use the click chemistry of Azide - Alkyne 1,3 - dipolar cycloaddition reaction via i to i + 4 intramolecular side-chain to side-chain cycloaddition or intermolecular side-chain to side-chain connection to carry out structural modification in different ways.The 1,4 - disubstituted [1,2,3] triazolyl-containing peptides includ the traditional natural of antimicrobial peptides Anoplin and MPI, obtained antimicrobial peptides having a novel structure of the C-Anoplin、C-MPI、J-AM,、J-AA and J-MM. The antibacterial activity, cytotoxicity, stability and multidrug resistance of these new peptides were evaluated, in order to get new structure antimicrobial peptides with high efficiency, low toxicity, stable and not prone to tolerance.First, we synthesized the desired fmoc-protected non-natural amino acid L-propargyl glycine (Fmoc-L-Pra-OH), then the solid phase synthesis and liquid phase synthesis method was used to obtain the target crude peptide, and then it was purified by reverse-phase efficient liquid phase (RP-HPLC). The minimum inhibitory concentration (MIC), hemolysis and resistance to proteolytic digestion characteristic, electron microscopy scanning, PI staining and multidrug resistance characteristic of the final product peptides were studied. The results shown that new peptides, J-AM and J-AA, have high antibacterial activity and anti-drug-resistant activity, but its stability is far from satisfactory.The result shows that the method of side chain cyclization using click chemistry structural modification of the natural peptide, reduced the hemolysis to a certain extent but reduced the antibacterial activity at the same time, and the side chain connected structural modification intermolecular enhanced the activity of the antimicrobial peptides, but did not increase proteolytic stability.These structure-activity relationship will help us for the further study on the application of click chemistry in the natural antimicrobial peptides structural modification. On the other hand, we assume that the cyclization in different locations and different locations to connect may have different results, more in-depth study is going on in our group.