Ultrashort Peptide Bioconjugates are Exclusively Antifungal Agents and Synergize with Cyclodextrin and Amphotericin B

摘要: Many natural broad-spectrum cationic antimicrobial peptides (AMPs) possess a general mode of action that is dependent on lipophilicity and charge. Modulating the AMPs by addition fatty acid has been an effective strategy to increase lytic activity can further broaden spectrum AMPs. However, lipophilic modifications narrow exclusively direct fungi are less common. Here, we show short peptide sequences be targeted with structured biomolecules, such as vitamin E cholesterol. The conjugates were active against Aspergillus fumigatus, Cryptococcus neoformans, Candida albicans but not bacteria observed cause membrane perturbation transmission electron microscopy in permeability studies. for C. albicans, selected compounds without cell membrane, synergism was seen conjugate amphotericin B. Moreover, combination β-cyclodextrin, antibacterial emerged compounds. Biocompatibility tested vitro vivo using toxicity assays erythrocytes, macrophages, mice. In cytotoxicity experiments led selective ratios (50% lethal concentration/MIC) up 64 highly antifungal compounds, no murine seen. Taken together, these results highlight importance conjugated structure suggest modulation other biologically relevant hydrophobic moieties, cholesterol E, generate unique bioactivity.