Structural characterization of a peptoid with lysine-like side chains and biological activity using NMR and computational methods.
Related Articles Structural characterization of a peptoid with lysine-like side chains and biological activity using NMR and computational methods.
Org Biomol Chem. 2013 Jan 28;11(4):640-7
Authors: Sternberg U, Birtalan E, Jakovkin I, Luy B, Schepers U, Bräse S, Muhle-Goll C
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.
PMID: 23223799 [PubMed - indexed for MEDLINE]
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