title: Relative helix-helix conformations in branched aromatic oligoamide foldamers.
abstract: The de novo design and synthesis of large and well-organized, tertiary-like, α-peptidic folded architectures is difficult because it relies on multiple cooperative interactions within and between secondary folded motifs of relatively weak intrinsic stability. The very stable helical structures of oligoamides of 8-amino-2-quinoline carboxylic acid offer a way to circumvent this difficulty thanks to their ability to fold into predictable and stable secondary motifs. Branched architectures comprised of two pairs of tetrameric (1), pentameric (2), or octameric (3) oligomers connected via an ethylene glycol spacer were designed and synthesized. The short spacer holds two helices in close proximity, thus enabling interactions between them. Degrees of freedom allowed in the system are well-defined: the relative P or M handedness of the two helices; the relative orientation of the helix axes; and the gauche or anti conformation of the ethylene spacer. Investigating the structures of 1-3 in the solid state and in solution allowed a detailed picture to be drawn of their conformational preferences and dynamics. The high variability of the solid state structures provides many snapshots of possible solution conformations. Helix-helix handedness communication was evidenced and shown to depend both on solvent and on a defined set of side chains at the helix-helix interface. Interdigitation of the side chains was found to restrict free rotation about the ethylene spacer. One solid state structure shows a high level of symmetry and provides a firm basis to further design specific side chain/side chain directional interactions.
authors.affiliation: Institut Européen de Chimie et Biologie, Université de Bordeaux-CNRS UMR5248 and UMS3033, 2 rue Robert Escarpit, 33607 Pessac, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Delsuc
authors.forename: Stéphane
authors.initials: S
authors.lastname: Massip
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Léger
authors.forename: Brice
authors.initials: B
authors.lastname: Kauffmann
authors.forename: Ivan
authors.initials: I
authors.lastname: Huc
mesh_terms: D000577:Amides / Q000737:chemistry*; D040761:Biomimetic Materials / Q000737:chemistry; D019855:Ethylene Glycol / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011804:Quinolines / Q000737:chemistry*
chemical_list: C558648:8-amino-2-quinoline carboxylic acid; D000577:Amides; D010455:Peptides; D011804:Quinolines; D019855:Ethylene Glycol