Cu reduces hemolytic activity of the antimicrobial peptide HMPI and enhances its trypsin resistance

Nowadays, drug-resistant microbes are becoming a serious clinical problem threatening people's health and life.Antimicrobial peptides (AMPs) are believed to be potential alternatives of conventional antibiotics to combat the threat of drug-resistant microbes.However, the susceptibility of AMPs toward proteases is one of the major problems limiting their clinical use.In the present study, we reported the effect of Cu 2+ on the bioactivity of AMP HMPI.We found that the addition of Cu 2+ could improve the protease resistance of AMP HMPI without affecting its bioactivity.Notably, after the binding of Cu 2+ with HMPI, the hemolytic activity of HMPI was greatly decreased.In addition, our results also demonstrated that the addition of Cu 2+ increased the production of reactive oxygen species in the fungal cells, which may be a supplement for the antifungal activity of HMPI.In conclusion, the introduction of Cu 2+ may provide an inorganic strategy to improve the stability and decrease the hemolytic activity of AMP HMPI, while maintaining its antifungal activity.