title: Helix-mediated protein--protein interactions as targets for intervention using foldamers.
abstract: Protein--protein interactions (PPIs) play a central role in virtually all biological processes and have been the focus of intense investigation from structural molecular biology to cell biology for the majority of the last two decades and, more recently, are emerging as important targets for pharmaceutical intervention. A common motif found at the interface of PPIs is the α-helix, suggesting that, in the same way as the "lock and key" model has evolved for competitive inhibition of enzymes, it should be possible to elaborate "rule-based" approaches for inhibition of helix-mediated PPIs. This review will describe the biological function and structural features of a series of representative helix-mediated PPIs and discuss approaches that are being developed to target these interactions with small molecules that employ non-natural amino acids.
authors.affiliation: Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, UK. T.A.Edwards@leeds.ac.uk
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Edwards
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wilson
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D002213:Capsid / Q000378:metabolism; D018797:Cell Cycle Proteins; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D057786:Peptidomimetics; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*; D025941:Protein Interaction Mapping; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry / Q000378:metabolism; D051880:Receptors, Notch / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism; D000099229:RE1-Silencing Transcription Factor
chemical_list: D000596:Amino Acids; D018797:Cell Cycle Proteins; D015700:HIV Envelope Protein gp41; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D010455:Peptides; D057786:Peptidomimetics; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D018160:Receptors, Cytoplasmic and Nuclear; D051880:Receptors, Notch; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D000099229:RE1-Silencing Transcription Factor; C497442:HIF1A protein, human; C482775:MDM4 protein, human; C497206:MDM2 protein, human