Effect of increasing positive charge on antimicrobial activity of aurein ۱.۲

Methods : The aurein ۱.۲ sequence (GLFDIIKKIAESF) was derived from the APD۳ database. A modified peptide was designed in which aspartic and glutamic acids were substituted with lysines. Their physicochemical properties and antimicrobial activities were predicted by ProtParam and CAMPR۳, respectively. The aurein ۱.۲ and modified peptide were synthesized with C-terminal amidation. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the peptides were determined by standard methods against Enterococcus faecalis and Staphylococcus aureus in the range of ۲۰۰ to ۰.۳۹ μg/ml of the peptides.Results : Amino acid substitutions increased the positive charge of the aurein ۱.۲ from +۱ to +۵, without changing its hydrophobicity (۵۳%). The results of bioinformatics prediction showed that the substitutions improved the antimicrobial property of the peptide. The MIC and MBC of the modified peptide were equal and they were ۱۲.۵ and ۲۵ μg/ml for S. aureus and E. faecalis, respectively. However, the MIC and MBC values of aurein ۱.۲ were ۲۵ and ۵۰ μg/ml for S. aureus and E. faecalis, respectively.Conclusion : The beneficial effect of increasing positive charge on the antibacterial activity of peptides has been reported on several researches. Here, the studied substitutions decreased the MIC and MBC values for Gram-positive bacteria. The modified peptide can be used as a new drug candidate.

کلیدواژه ها:

Aurein ۱.۲ ، Cationic peptide ، Rational design