title: Design of NK-2-derived peptides with improved activity against equine sarcoid cells.
abstract: Equine sarcoid is a topically accessible model for the evaluation of anticancer peptides acting by physical membrane disruption avoiding the complexity of a systemic application. We aim at evaluating and improving natural peptides for host defence as lead structures, where we focus on the cationic and amphipathic peptide NK-2. Cytotoxicity tests, fluorescence microscopy and a chip-based biosensor, which enabled real-time monitoring of cell metabolism, were applied. Cancer cell killing was dynamic with an initial phase of increased cellular respiration, followed by membrane destruction. NK-2 was substantially improved and shortened. Novel peptides exhibited a fivefold improved activity against sarcoid cells, while haemolysis remained almost unaltered. Similar Zeta potential and similar amount of surface phosphatidylserine of sarcoid and normal skin cells are responsible for a lack of selectivity between these two cell types.
authors.affiliation: Division of Biophysics, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, D-23845, Borstel, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gross
authors.forename: Dominik
authors.initials: D
authors.lastname: Wilms
authors.forename: Jannike
authors.initials: J
authors.lastname: Krause
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
authors.forename: Jörg
authors.initials: J
authors.lastname: Andrä
mesh_terms: D000818:Animals; D015374:Biosensing Techniques; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D006461:Hemolysis; D006736:Horses / Q000821:virology*; D006801:Humans; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010718:Phosphatidylserines / Q000737:chemistry; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D010455:Peptides; D010718:Phosphatidylserines; C475945:peptide NK-2
keywords: Zeta potential; antimicrobial peptide; membrane; phosphatidylserine; pore formation; skin cancer