Lipidation of Temporin-1CEb Derivatives as a Tool for Activity Improvement, Pros and Cons of the Approach

The alarming raise of multi-drug resistance among human microbial pathogens makes the development novel therapeutics a priority task. In contrast to conventional antibiotics, antimicrobial peptides (AMPs), besides evoking broad spectrum activity against microorganisms, could offer additional benefits, such as ability neutralize toxins, modulate inflammatory response, eradicate bacterial and fungal biofilms or prevent their development. latter properties are special interest, most antibiotics available on market have limited diffuse through rigid structures biofilms. Lipidation AMPs is considered an effective approach for enhancement potential in vivo stability; however, it also undesired impact selectivity, solubility aggregation state modified peptides. present work, we describe results structural modifications compounds designed based cationic DK5 CAR-PEG-DK5, derivatized at N-terminal part with fatty acids different lengths carbon chain. proposed substantially improved final effectiveness inhibition biofilm well eradication pre-formed 24 h old Candida albicans Staphylococcus aureus. active (C5-DK5, C12-DK5 C12-CAR-PEG-DK5) were potent resistant aureus USA300 strain clinical isolates Pseudomonas aeruginosa. Both experimental silico methods revealed strong correlation between length acid attached membranolytic properties, tendency self-assemble cytotoxicity.