Design And Activity Studies Of The Novel Antimicrobial Peptides With Wound Healing-promoting Properties

Infected wounds cause delay in wound closure and impose significantly negative effects on patient care and recovery.Antimicrobial peptides(AMPs)with anti-microbial and wound closure activities,along with little opportunity for the development of resistance,represent one of the promising agents for new therapeutic approaches in the infected wound treatment.In the study,we hope to construct and screen antimicrobial peptides with antimicrobial and wound-healing properties which provide reference for development of wound healing-promoting peptides.The neuropeptide substance P(SP)displays wound healing-promoting activities.However,the previous research has indicated that SP did not have antimicrobial activities against the common clinical pathogenic bacteria.Therefore,according to characteristics of AMPs,we regarded SP containing hydrophobic residues as C-terminal of AMPs,and dynorphin(DYN)rich in arginine and lysine as N-terminal of AMPs.Then,we designed and synthesized a series of analogues(BA-17～BA-30)by connecting the active regions of SP and DYN and replacing certain amino acids to obtain the antimicrobial peptides with wound healing-promoting properties.At first,we evaluated antimicrobial activities of these analogues against common clinical pathogenic bacteria.The results showed that BA-19,BA-20,BA-22,BA-29 and BA-30 occupied antimicrobial activities against multidrug-resistant bacteria.Furthermore,these compounds inhibited S.aureus biofilm formation at low concentrations.In the mechanism studies,the analogues killed bacteria not only by disrupting the membrane but also by binding to DNA.Moreover,the analogues had low haemolysis activity.In the studies about promoting wound healing activity,the five screened analogues had been explored.The results indicated BA-22 promoted cell proliferation,and BA-22 and BA-30 induced cell migration.Next,the five analogues were evaluated in vivo.BA-22 and BA-30 can accelerate wound healing of mice similar to SP.In conclusion,we have identified BA-22 with potent antimicrobial activities,low cytotoxicity and wound-healing properties.Moreover,BA-22 killed bacteria by double-target,which was difficult for bacteria to develop resistance.Thus,BA-22 could be explored in depth as a candidate compound.These results provided a new strategy for the chronic wounds treatment.