title: Coiled-Coil-Mediated Activation of Oligoarginine Cell-Penetrating Peptides.
abstract: A supramolecular approach was undertaken to create functionally activatable cell-penetrating peptides. Two tetra-arginines were assembled into an active cell-penetrating peptide by heterodimerizing leucine zippers. Three different leucine-zipper pairs were evaluated: activation was found to depend on the association constant of the coiled-coil peptides. The weaker-binding peptides required an additional disulfide linkage to induce cell-penetrating capability, whereas for the most-stable coiled-coil no additional stabilization was needed. The latter zipper pair was used to show that the induced formation of the coiled coils allows control over the uptake of an oligoarginine CPP-conjugated cargo protein.
authors.affiliation: Bio-Organic Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.
authors.forename: Saskia A
authors.initials: SA
authors.lastname: Bode
authors.affiliation: Bio-Organic Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.|Biomolecular Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.
authors.forename: Ilmar C
authors.initials: IC
authors.lastname: Kruis
authors.affiliation: Bio-Organic Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.
authors.forename: Hans P J H M
authors.initials: HP
authors.lastname: Adams
authors.affiliation: Biomolecular Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.
authors.forename: Wilbert C
authors.initials: WC
authors.lastname: Boelens
authors.affiliation: Biomolecular Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Pruijn
authors.affiliation: Bio-Organic Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.
authors.forename: Jan C M
authors.initials: JC
authors.lastname: van Hest
authors.affiliation: Bio-Organic Chemistry, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ, Nijmegen, Netherlands.
authors.forename: Dennis W P M
authors.identifier: http://orcid.org/0000-0002-9284-837X
authors.initials: DW
authors.lastname: Löwik
mesh_terms: D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism*; D002942:Circular Dichroism; D019281:Dimerization; D004705:Endocytosis; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D016350:Leucine Zippers; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D009842:Oligopeptides; D001120:Arginine; D016650:Fluorescein-5-isothiocyanate
keywords: activatable cellular uptake; cell-penetrating peptides; drug delivery; fluorescent probes; leucine zippers; noncovalent conjugation