title: Probing Protein Surfaces: QSAR Analysis with Helix Mimetics.
abstract: α-Helix-mediated protein-protein interactions (PPIs) are important targets for small-molecule inhibition; however, generic approaches to inhibitor design are in their infancy and would benefit from QSAR analyses to rationalise the noncovalent basis of molecular recognition by designed ligands. Using a helix mimetic based on an oligoamide scaffold, we have exploited the power of a modular synthesis to access compounds that can readily be used to understand the noncovalent determinants of hDM2 recognition by this series of cell-active p53/hDM2 inhibitors.
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: Valeria
authors.initials: V
authors.lastname: Azzarito
authors.affiliation: Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.|School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Rowell
authors.affiliation: Department of Chemistry, Imperial College London, London, London, SW7 2AZ, UK.|Institue of Chemical Biology, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Barnard
authors.affiliation: Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.|School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Edwards
authors.affiliation: Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.|School of Molecular and Cellular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Macdonald
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: Stuart L
authors.initials: SL
authors.lastname: Warriner
authors.affiliation: School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. S.L.Warrriner@leeds.ac.uk.|Astbury Centre For Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK. S.L.Warrriner@leeds.ac.uk.
authors.forename: Andrew J
authors.identifier: http://orcid.org/0000-0001-9852-6366
authors.initials: AJ
authors.lastname: Wilson
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D017433:Protein Structure, Secondary; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013499:Surface Properties; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D008024:Ligands; D054852:Small Molecule Libraries; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: chemical biology; foldamers; helix mimetics; p53/hDM2; protein-protein interactions