title: A tailor-made specific anion-binding motif in the side chain transforms a tetrapeptide into an efficient vector for gene delivery.
abstract: Arginine-rich cell-penetrating peptides are widely utilized as vectors for gene delivery. However, their transfection efficacy still needs to be optimized. To accomplish this, guanidinocarbonylpyrrole groups, which are tailor-made anion binding sites, were introduced into the side chains of tetralysine to obtain the peptide analogue 1. In contrast to the common strategy of adding a lipophilic tail to peptide vectors, this novel method most likely enhances transfection efficacy through more specific interactions between the binding motifs and DNA or the cell membrane. Tetrapeptide analogue 1 is thus the smallest peptidic transfection vector that has been reported to date. The transfection efficacy of 1, which on average has less than two positive charges under physiological conditions, is even better than that of polyethylenimine (PEI). Furthermore, 1 exhibits only negligible cytotoxicity, which makes it an interesting candidate for further development.
authors.affiliation: Institute for Organic Chemistry, University of Duisburg-Essen, 45117 Essen (Germany).
authors.forename: Mao
authors.initials: M
authors.lastname: Li
authors.forename: Stefanie
authors.initials: S
authors.lastname: Schlesiger
authors.forename: Shirley K
authors.initials: SK
authors.lastname: Knauer
authors.forename: Carsten
authors.initials: C
authors.lastname: Schmuck
mesh_terms: D000838:Anions / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry*
chemical_list: D000838:Anions; D009842:Oligopeptides
keywords: anion binding; cell-penetrating peptides; gene delivery; gene technology; transfection