The invention provides a
Protegrin-1
antimicrobial peptide derivative and a preparation method and application thereof. The preparation method of the
Protegrin-1
antimicrobial peptide derivative comprises the steps that linear polypeptide is synthesized; the linear polypeptide is synthesized into
cyclase polypeptide, the Cys in the fifth position and the fourth position and the Cys in the seventh position and the twelfth position of the
amino acid sequence in the
cyclase polypeptide form two pairs of disulfide bonds. According to the
Protegrin-1
antimicrobial peptide derivative and the preparation method and the application thereof, molecule improvement is performed on the Protegrin-1 antimicrobial peptide by replacing
amino acid in corresponding positions, the
antibacterial peptide derivative which is high in
antibacterial activity, low in hemolytic activity and more stable in
protease is screened by a lot of activity experiments, the artificial synthesis of the group of antibacterial peptides is simple and the cost is lower, the derivative is beneficial for industrial production, and excellent candidate peptides are provided for the research and development of novel antibacterial agents.