Determination of antifungal activity and action mechanism of the modified Aurein ۱.۲ peptide derivatives

Background and Objectives: With the emergence of drug-resistant fungi and the increased population prone to fungal infections, more effective antifungal drugs are needed. Aurein ۱.۲ is a potent antimicrobial peptide. Here, we designed a novel derivative of Aurein ۱.۲, called Aurein N۳, which is a modified form of Aurein N۲ (another Aurein ۱.۲ derivative), in which Lys ۸ residue was replaced with Leu ۱۳, and was also modified by creating two other mutations.Methods and Materials:Aurein N۳ was designed using several algorithms and docking studies.All peptides were synthesized and some of their bio-activity indices:antifungal properties on ۱۱ fungicytotoxicityhemolysis, and time of the killing were investigated.Electron microscopy, lived/dead staining, and ergosterol binding assay were performed to study their mechanism of action.Findings:Peptide design and bioinformatics studiesPeptides-ergosterol docking simulationMIC and MFC of peptidesKilling time of peptidesMTT assay resultsHemolytic activity of peptidesRegarding the results of the Ergo sterol assay, all three peptides Aurein N۲, Aurein N۳, and Aurein ۱.۲ was able to bind to ergo sterol.Conclusions: In the present study, we designed a novel derivate of Aurein ۱.۲ peptide with previously confirmed antifungal activities. This novel derivative, called Aurein N۳, is a modified form of Aurein N۲ in which lys ۸ residue was replaced with Leu ۱۳, and also two mutations G۱: I۱ and I۶: K۶ were mounted in its sequence.

کلیدواژه ها:

In silico drug design ، Antimicrobial peptides ، Antifungal peptides Aurein ۱.۲