title: Computational Prediction and Rationalization, and Experimental Validation of Handedness Induction in Helical Aromatic Oligoamide Foldamers.
abstract: Metadynamics simulations were used to describe the conformational energy landscapes of several helically folded aromatic quinoline carboxamide oligomers bearing a single chiral group at either the C or N terminus. The calculations allowed the prediction of whether a helix handedness bias occurs under the influence of the chiral group and gave insight into the interactions (sterics, electrostatics, hydrogen bonds) responsible for a particular helix sense preference. In the case of camphanyl-based and morpholine-based chiral groups, experimental data confirming the validity of the calculations were already available. New chiral groups with a proline residue were also investigated and were predicted to induce handedness. This prediction was verified experimentally through the synthesis of proline-containing monomers, their incorporation into an oligoamide sequence by solid phase synthesis and the investigation of handedness induction by NMR spectroscopy and circular dichroism.
authors.affiliation: Department of Chemistry & Biochemistry, University of the Sciences, 600 South 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: University of Bordeaux, CBMN (UMR 5248), Institut Européen de Chimie et Biologie, 2 rue Escarpit, 33600, Pessac, France.|CNRS, CBMN (UMR 5248), France.|Bordeaux Institut National Polytechnique, CBMN (UMR 5248), France.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Chemistry & Biochemistry, University of the Sciences, 600 South 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Ara M
authors.initials: AM
authors.lastname: Abramyan
authors.affiliation: Servier Research Institute of Medicinal Chemistry, Záhony utca 7., 1031, Budapest, Hungary.
authors.forename: Ádám
authors.initials: Á
authors.lastname: Mészáros
authors.affiliation: Servier Research Institute of Medicinal Chemistry, Záhony utca 7., 1031, Budapest, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Csékei
authors.affiliation: Servier Research Institute of Medicinal Chemistry, Záhony utca 7., 1031, Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Kotschy
authors.affiliation: University of Bordeaux, CBMN (UMR 5248), Institut Européen de Chimie et Biologie, 2 rue Escarpit, 33600, Pessac, France.|CNRS, CBMN (UMR 5248), France.|Bordeaux Institut National Polytechnique, CBMN (UMR 5248), France.
authors.forename: Ivan
authors.identifier: http://orcid.org/0000-0001-7036-9696
authors.initials: I
authors.lastname: Huc
authors.affiliation: Department of Chemistry & Biochemistry, University of the Sciences, 600 South 43rd Street, Philadelphia, PA, 19104, USA.
authors.forename: Vojislava
authors.initials: V
authors.lastname: Pophristic
keywords: aromatic oligoamides; computational chemistry; foldamers; helical structures; metadynamics