title: Beta-peptides with improved affinity for hDM2 and hDMX.
abstract: We previously described a series of 3(14)-helical beta-peptides that bind the hDM2 protein and inhibit its interaction with a p53-derived peptide in vitro. Here we present a detailed characterization of the interaction of these peptides with hDM2 and report two new beta-peptides in which non-natural side chains have been substituted into the hDM2-recognition epitope. These peptides feature both improved affinity and inhibitory potency in fluorescence polarization and ELISA assays. Additionally, one of the new beta-peptides also binds the hDM2-related protein, hDMX, which has been identified as another key therapeutic target for activation of the p53 pathway in tumors.
authors.affiliation: Department of Chemistry, Yale University, New Haven, CT 06520, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Harker
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Daniels
authors.forename: Danielle A
authors.initials: DA
authors.lastname: Guarracino
authors.forename: Alanna
authors.initials: A
authors.lastname: Schepartz
mesh_terms: D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005454:Fluorescence Polarization; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / 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; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2