title: Structural characterization of a peptoid with lysine-like side chains and biological activity using NMR and computational methods.
abstract: N-substituted glycine oligomers or peptoids with charged side chains are a novel class of cell penetrating peptide mimetics and have been shown to serve as drug delivery agents. Here, we investigated by NMR spectroscopy and quantum chemical calculations whether a Rhodamine B labelled peptoid [RhoB(Spiro)-Ahx]-[But](6A)NH(2) with lysine-like side chains adopts structural motifs similar to regular peptides. Due to a low chemical shift dispersion, high resolution structure determination with conventional NMR-derived distance restraints and J-couplings was not possible. Instead, a combined assignment and structure refinement strategy using the QM/MM force field COSMOS-NMR was developed to interpret the highly ambiguous chemical shift and distance constraints and obtain a medium resolution three-dimensional structural model. This allowed us to select for the all cis-amide conformation of the peptide with a pseudo-helical arrangement of extended side chains as a faithful representative structure of [RhoB(Spiro)-Ahx]-[But](6A)NH(2). We tested the biological activity of the peptoid by live-cell imaging, which showed that the cellular uptake of the peptoid was comparable to conventional cell-penetrating peptides.
authors.affiliation: Karlsruhe Institute of Technology (KIT), POB 3640, D-76021 Karlsruhe, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sternberg
authors.forename: Esther
authors.initials: E
authors.lastname: Birtalan
authors.forename: Igor
authors.initials: I
authors.lastname: Jakovkin
authors.forename: Burkhard
authors.initials: B
authors.lastname: Luy
authors.forename: Ute
authors.initials: U
authors.lastname: Schepers
authors.forename: Stefan
authors.initials: S
authors.lastname: Bräse
authors.forename: Claudia
authors.initials: C
authors.lastname: Muhle-Goll
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008239:Lysine; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D057054:Molecular Imaging; D034444:Peptoids / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D034444:Peptoids; D008239:Lysine