title: Solid-phase synthesis, bioconjugation, and toxicology of novel cationic oligopeptoids for cellular drug delivery.
abstract: For many therapeutic applications, it has become more and more important to find synthetic compounds that have the ability to transport a variety of drugs and cargo molecules into cells and tissues. Like arginine-rich cell-penetrating peptides (CPPs), it is already known that peptide mimetics such as beta-peptides and peptoids can also express a transport function. In this study, ten fluorophore-labeled chiral and achiral peptoids with different backbone lengths and side chains as well as three peptoids coupled to a therapeutically active porphyrin moiety were prepared using a highly modular solid-phase synthesis (SPP) approach. To compare the structural determinants with the cellular uptake efficiency, all peptoids were analyzed by live cell imaging. All cells show an even vesicular distribution of the internalized peptoids, also revealing that a vesicular escape into the cytosol was stronger for peptoids with longer backbones. Moreover, the uptake efficiency correlated with both the incubation time and the given concentration. Toxicology tests and uptake experiments with porphyrin-coupled peptoids indicate their suitability for application as robust and readily available drug delivery systems or intracellular probes.
authors.affiliation: Institut für Organische Chemie and Center for Functional Nanostructures, Universität Karlsruhe TH, Karlsruhe, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Schröder
authors.forename: Katja
authors.initials: K
authors.lastname: Schmitz
authors.forename: Nicole
authors.initials: N
authors.lastname: Niemeier
authors.forename: Teodor S
authors.initials: TS
authors.lastname: Balaban
authors.forename: Harald F
authors.initials: HF
authors.lastname: Krug
authors.forename: Ute
authors.initials: U
authors.lastname: Schepers
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
mesh_terms: D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000493:pharmacokinetics; D019556:COS Cells / Q000187:drug effects; D002463:Cell Membrane Permeability; D002478:Cells, Cultured / Q000187:drug effects; D002522:Chlorocebus aethiops; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D034444:Peptoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011487:Protein Conformation
chemical_list: D016895:Culture Media, Serum-Free; D004337:Drug Carriers; D009842:Oligopeptides; D034444:Peptoids; D001120:Arginine