The activity of LE10 peptide on biological membranes using molecular dynamics, in vitro and in vivo studies

Cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs) are generally defined as small cationic peptides with the ability to interact with lipidic membranes, in a process driven by electrostatic and hydrophobic processes. The interaction with CPPs is known to lead to its translocation across the membrane, while with AMPs lead to membrane damage.Here we present one synthetic anionic peptide, LE10 (LELELELELELELELELELE), which strongly interacts with model membranes, showing properties of CPPs (translocation through lipidic membranes on a mechanism usually described for cationic CPPs) and AMPs (membrane disruption) in molecular dynamic studies, experimental studies with liposomes and mammalian cells in vitro.Based on the LE10 properties here demonstrated, small modifications in its structure could make it a very promising tool for drug delivery.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Strong interaction between the peptide and membrane models in molecular simulations. ► Experimental results in agreement with simulations behavior. ► High concentration of peptide leads to liposome disruption and mammalian cell dead. ► One more argument for the classification of membrane active peptides. ► Positive net-charge is not an essential feature of membrane active peptides.