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EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide

Eissa, N.G., Sayers, E.J., Birch, D., Patel, S.G., Tsai, Y.-H., Nielsen, H. Mørck and Jones, Arwyn 2020. EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide. Biochemical Journal 477 (1) , pp. 45-60. 10.1042/BCJ20190452
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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Pharmacy
Chemistry
Publisher: Portland Press
ISSN: 0264-6021
Date of First Compliant Deposit: 20 January 2020
Date of Acceptance: 10 December 2019
Last Modified: 21 Jan 2020 11:50
URI: http://orca.cf.ac.uk/id/eprint/128803

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