EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide. Issue 1 (8th January 2020)

• Record Type: Journal Article
• Authors: Eissa, N.G.; Sayers, E.J.; Birch, D.; Patel, S.G.; Tsai, Y.-H.; Nielsen, H. Mørck; Jones, A.T.
• Is Part Of: Biochemical journal. Volume 477:Issue 1(2020)
• Page Start: 45
• Page End: 60
• Publication Date: 2020-01-08
• Subjects: confocal microscopy -- drug delivery -- flow cytometry -- mammalian cell lines -- membrane-active peptide -- protein delivery; Biochemistry -- Periodicals; 572
• DOI: 10.1042/BCJ20190452
• Languages: English
• ISSNs: 0264-6021

Abstract

Abstract : Membrane-active peptides have been extensively studied to probe protein–membrane interactions, to act as antimicrobial agents and cell-penetrating peptides (CPPs) for the delivery of therapeutic agents to cells. Hundreds of membrane-active sequences acting as CPPs have now been described including bioportides that serve as single entity modifiers of cell physiology at the intracellular level. Translation of promising CPPs in pre-clinical studies have, however, been disappointing as only few identified delivery systems have progressed to clinical trials. To search for novel membrane-active peptides a sequence from the EGFR juxtamembrane region was identified (named EJP18), synthesised, and examined in its L- and D-form for its ability to mediate the delivery of a small fluorophore and whole proteins to cancer cell lines. Initial studies identified the peptide as being highly membrane-active causing extensive and rapid plasma membrane reorganisation, blebbing, and toxicity. At lower, non-toxic concentrations the peptides outperformed the well-characterised CPP octaarginine in cellular delivery capacity for a fluorophore or proteins that were associated with the peptide covalently or via ionic interactions. EJP18 thus represents a novel membrane-active peptide that may be used as a naturally derived model for biophysical protein–membrane interactions or for delivery of cargo into cells for therapeutic or diagnostic applications.