title: Structural characterizations of oligopyridyl foldamers, α-helix mimetics.
abstract: Protein-protein interactions are central to many biological processes, from intracellular communication to cytoskeleton assembly, and therefore represent an important class of targets for new therapeutics. The most common secondary structure in natural proteins is an α-helix. Small molecules seem to be attractive candidates for stabilizing or disrupting protein-protein interactions based on α-helices. In our study, we assessed the ability of oligopyridyl scaffolds to mimic the α-helical twist. The theoretical as well as experimental studies (X-ray diffraction and NMR) on conformations of bipyridines in the function of substituent and pyridine nitrogen positions were carried out. Furthermore, the experimental techniques showed that the conformations observed in bipyridines are maintained within a longer oligopyridyl scaffold (quaterpyridines). The alignment of the synthesized quaterpyridine with two methyl substituents showed that it is an α-helix foldamer; their methyl groups overlap very well with side chain positions, i and i + 3, of an ideal α-helix.
authors.affiliation: Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, FR CNRS INC3M, UFR des Sciences Pharmaceutiques, Université de Caen, bd Becquerel, 14032 Caen Cedex, France. jana.sopkova@unicaen.fr
authors.forename: Jana Sopkova-de Oliveira
authors.initials: JS
authors.lastname: Santos
authors.forename: Anne Sophie
authors.initials: AS
authors.lastname: Voisin-Chiret
authors.forename: Gregory
authors.initials: G
authors.lastname: Burzicki
authors.forename: Laure
authors.initials: L
authors.lastname: Sebaoun
authors.forename: Muriel
authors.initials: M
authors.lastname: Sebban
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Lohier
authors.forename: Rémi
authors.initials: R
authors.lastname: Legay
authors.forename: Hassan
authors.initials: H
authors.lastname: Oulyadi
authors.forename: Ronan
authors.initials: R
authors.lastname: Bureau
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
mesh_terms: D032701:Biomimetics / Q000379:methods*; D058105:Polymerization; D017433:Protein Structure, Secondary; D011506:Proteins / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D011506:Proteins; D011725:Pyridines