title: An α-Helix-Mimicking 12,13-Helix: Designed α/β/γ-Foldamers as Selective Inhibitors of Protein-Protein Interactions.
abstract: A major current challenge in bioorganic chemistry is the identification of effective mimics of protein secondary structures that act as inhibitors of protein-protein interactions (PPIs). In this work, trans-2-aminocyclobutanecarboxylic acid (tACBC) was used as the key β-amino acid component in the design of α/β/γ-peptides to structurally mimic a native α-helix. Suitably functionalized α/β/γ-peptides assume an α-helix-mimicking 12,13-helix conformation in solution, exhibit enhanced proteolytic stability in comparison to the wild-type α-peptide parent sequence from which they are derived, and act as selective inhibitors of the p53/hDM2 interaction.
authors.affiliation: CP3A Organic Synthesis Group, ICMMO, CNRS, Université Paris Sud, Université Paris Saclay, 15 Rue George Clemenceau, 91405, Orsay Cedex, France.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Grison
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.|Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Miles
authors.affiliation: CP3A Organic Synthesis Group, ICMMO, CNRS, Université Paris Sud, Université Paris Saclay, 15 Rue George Clemenceau, 91405, Orsay Cedex, France.|UFR Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, 4 Avenue de l'Observatoire, 75270, Paris cedex 06, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Robin
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. A.J.Wilson@leeds.ac.uk.|Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. A.J.Wilson@leeds.ac.uk.
authors.forename: Andrew J
authors.identifier: 0000-0001-9852-6366
authors.initials: AJ
authors.lastname: Wilson
authors.affiliation: CP3A Organic Synthesis Group, ICMMO, CNRS, Université Paris Sud, Université Paris Saclay, 15 Rue George Clemenceau, 91405, Orsay Cedex, France. david.aitken@u-psud.fr.
authors.forename: David J
authors.initials: DJ
authors.lastname: Aitken
mesh_terms: D002264:Carboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D003503:Cyclobutanes / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D011485:Protein Binding / Q000187:drug effects; D000072756:Protein Conformation, alpha-Helical / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
chemical_list: C542744:2-aminocyclobutanecarboxylic acid; C433227:CNBP protein, human; D002264:Carboxylic Acids; D003503:Cyclobutanes; D016601:RNA-Binding Proteins; D016159:Tumor Suppressor Protein p53
keywords: foldamers; inhibitors; peptidomimetics; protein-protein interactions; α-helix mimetics