Structure-function investigation of a novel dendrimeric and lipidated antimicrobial peptide

Antimicrobial peptides are usually polycationic and amphiphilic with high affinity for bacterial membranes. In order to characterize their therapeutic potential it is crucial to disclose which properties of the peptide/lipids are important for target selectivity, and to examine the peptide structure and its association with lipid bilayers. In this work, first experiments have been carried out on a promising peptide called SB056, which might represent the basis for developing a novel class of antibiotics. With the goal of enhancing the activity of a new semi-synthetic sequence, two identical peptides (WKKIRVRLSA) were assembled via a lysine-linker, carrying also an octanoyl-lipid anchor. A highly active compound was obtained, but its structure and mode-of-action remain unexplored. This dendrimeric peptide and its linear deca-peptide counterpart are being studied in parallel to highlight the relevant properties and differences between dendrimeric structure and the sequence. Monolayer intercalation is investigated with microtensiometry, Fluorescence spectroscopy is applied to study thermodynamics and kinetics of the binding process. Circular dichroism, NMR and MDsimulations are employed with the aimof elucidating the 3D structure in the membrane-bound state.