Study On The Design And Activity Of Antimicrobial Peptides Derived From Dynorphin

In recent years,the increasing frequency of antibiotic resistance among microorganisms has become a global problem,and a serious threat to human health.The antibacterial peptides(AMPs)with potent antimicrobial activity and unique membrane mechanism of action have attracted more attention.They are expected to become candidates for new antibiotic and greatly improve the status of treatment of bacterial infections.Neuropeptides(NPs)are ubiquitous in nerve cells or tissues.They have multiple biological activities,such as signal transport,immunomodulation and antibacterial activity.Dynorphin(DYN)was found in 1979,which takes part in behavioral regulation and can penetrate into neurons and non-neuronal cells.It is similar to AMPs in structure properties.Based on the similar structure and crossed function of AMPs and NPs,we designed a series of BA antibacterial analogues.Through the antibacterial activity and cytotoxicity screening of these analogues,it was found that the vast majority analogues retain low toxicity of the parent peptide,and showed higher antibacterial activity compared to DYN.Simultaneously,study on the representative analogues like BA-100/BA-84,BA-48/BA-52,BA-61/BA-85,BA-37/BA-83,BA-39/BA-87 and BA-34/BA-103 showed that hydrophobic as an important physical and chemical parameters.It affected the rate of sterilization of analogues,and changes the appropriate range could make analogues between P.aeruginosa 27853 and S.aureus 25923 showing the difference in activity,even if the bacteria lose the cell wall can not eliminate this difference.Finally,according to the preference of the activity in P.aeruginosa 27853 and S.aureus 25923,we selected BA-100,BA-83 and BA-103 as representative analogues to further study.Through the mechanism and application research of these analogues,we found that BA analogues can selectively kill bacteria by membrane lysis mechanism,and inhibit P.aeruginosa 27853 or S.aureus 25923 biofilm formation at low concentrations.In addition,it also can damage S.aureus 25923 biofilm at high concentrations.In conclusion,we studied on the antibacterial activity and mechanism or application research of these BA analogues.It expanded the antimicrobial peptide type,and which was of great significance to reduce the impact of bacterial resistance mechanism.