title: Exploring helical folding of oligoureas during chain elongation by high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy.
abstract: The development of novel folding oligomers (foldamers) for biological and biomedical applications requires both precise structural information and appropriate methods to detect folding propensity. However, the synthesis and the systematic conformational investigation of large arrays of oligomers to determine the influence of factors, such as chain length, side chains, and surrounding environment, on secondary structure can be quite tedious. Herein, we show for 2.5-helical N,N'-linked oligoureas (gamma-peptide lineage) that the whole process of foldamer characterization can be accelerated by using high-resolution magic-angle-spinning (HRMAS) NMR spectroscopy. This was achieved by monitoring a simple descriptor of conformational homogeneity (e.g., chemical shift difference between diastereotopic main chain CH2 protons) at different stages of oligourea chain growth on a solid support. HRMAS NMR experiments were conducted on two sets of oligoureas, ranging from dimer to hexamer, immobilized on DEUSS, a perdeuterated poly(oxyethylene)-based solid support swollen in solvents of low to high polarity. One evident advantage of the method is that only minute amount of material is required. In addition, the resonance of the deuterated resin is almost negligeable. On-bead NOESY spectra of high quality and with resolution comparable to that of liquid samples were obtained for longer oligomers, thus allowing detailed structural characterization.
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunologie et Chimie Thérapeutiques, 15 rue Descartes, 67084 Strasbourg, France.
authors.forename: Aude
authors.initials: A
authors.lastname: Violette
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lancelot
authors.forename: Alexander
authors.initials: A
authors.lastname: Poschalko
authors.forename: Martial
authors.initials: M
authors.lastname: Piotto
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Briand
authors.forename: Jesus
authors.initials: J
authors.lastname: Raya
authors.forename: Karim
authors.initials: K
authors.lastname: Elbayed
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
authors.forename: Gilles
authors.initials: G
authors.lastname: Guichard
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012997:Solvents; D014508:Urea / Q000737:chemistry*
chemical_list: D012997:Solvents; D014508:Urea