title: Propensity for local folding induced by the urea fragment in short-chain oligomers.
abstract: Examination of local folding and H-bonding patterns in model compounds can be extremely informative to gain insight into the propensity of longer-chain oligomers to adopt specific folding patterns (i.e. foldamers) based on remote interactions. Using a combination of experimental techniques (i.e. X-ray diffraction, FT-IR absorption and NMR spectroscopy) and theoretical calculations at the density functional theory (DFT) level, we have examined the local folding patterns induced by the urea fragment in short-chain aza analogues of beta- and gamma-amino acid derivatives. We found that the urea-turn, a robust C(8) conformation based on 1<--3 H-bond interaction, is largely populated in model ureidopeptides (I-IV) obtained by replacing the alpha-carbon of a beta-amino acid by a nitrogen. This H-bonding scheme is likely to compete with remote H-bond interactions, thus preventing the formation of secondary structures based on remote intrastrand interactions in longer oligomers. In related oligomers obtained by the addition of a methylene in the main chain (V-VIII), nearest-neighbour H-bonded interactions are unfavourable i.e. the corresponding C9 folding pattern is hardly populated. In this series, folding based on remote intrastrand interactions becomes possible for longer oligomers. We present spectroscopic evidence that tetraurea VIII is likely to be the smallest unit capable of reproducing the H-bonded motif found in 2.5-helical N,N'-linked oligoureas.
authors.affiliation: CNRS, Institut de Biologie Moléculaire et Cellulaire, Immunologie et Chimie Thérapeutiques, 15, rue Descartes, F-67000, Strasbourg, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Fischer
authors.forename: Claude
authors.initials: C
authors.lastname: Didierjean
authors.forename: Franck
authors.initials: F
authors.lastname: Jolibois
authors.forename: Vincent
authors.initials: V
authors.lastname: Semetey
authors.forename: Jose
authors.initials: J
authors.lastname: Manuel Lozano
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Briand
authors.forename: Michel
authors.initials: M
authors.lastname: Marraud
authors.forename: Romuald
authors.initials: R
authors.lastname: Poteau
authors.forename: Gilles
authors.initials: G
authors.lastname: Guichard
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000577:Amides / Q000737:chemistry; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D011789:Quantum Theory; D017550:Spectroscopy, Fourier Transform Infrared; D014508:Urea / Q000737:chemistry*
chemical_list: D000475:Alkenes; D000577:Amides; D010455:Peptides; D014508:Urea