title: Proximity-enabled bioreactivity to generate covalent peptide inhibitors of p53-Mdm4.
abstract: Although small molecule covalent inhibitors have been widely explored, macromolecular covalent inhibitors are more difficult to design and implement. Here we present a strategy to enable a peptide to bind to its target protein covalently via proximity-enabled bioreactivity, improving its activity of inhibiting the p53-Mdm4 interaction by 10-fold.
authors.affiliation: Department of Pharmaceutical Chemistry and the Cardiovascular Research Institute, University of California, San Francisco, 555 Mission Bay Blvd South, San Francisco, CA 94158, USA. Lei.Wang2@ucsf.edu.
authors.forename: Christian
authors.initials: C
authors.lastname: Hoppmann
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps / Q000187:drug effects*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53