title: Stapled peptides with improved potency and specificity that activate p53.
abstract: By using a phage display derived peptide as an initial template, compounds have been developed that are highly specific against Mdm2/Mdm4. These compounds exhibit greater potency in p53 activation and protein-protein interaction assays than a compound derived from the p53 wild-type sequence. Unlike Nutlin, a small molecule inhibitor of Mdm2/Mdm4, the phage derived compounds can arrest cells resistant to p53 induced apoptosis over a wide concentration range without cellular toxicity, suggesting they are highly suitable for cyclotherapy.
authors.affiliation: p53 Laboratory (p53Lab, A*STAR), 8A Biomedical Grove, #06-06, Immunos, Singapore 138648. cjbrown@p53lab.a-star.edu.sg
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Brown
authors.forename: Soo T
authors.initials: ST
authors.lastname: Quah
authors.forename: Janice
authors.initials: J
authors.lastname: Jong
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Goh
authors.forename: Poh C
authors.initials: PC
authors.lastname: Chiam
authors.forename: Kian H
authors.initials: KH
authors.lastname: Khoo
authors.forename: Meng L
authors.initials: ML
authors.lastname: Choong
authors.forename: May A
authors.initials: MA
authors.lastname: Lee
authors.forename: Larisa
authors.initials: L
authors.lastname: Yurlova
authors.forename: Kourosh
authors.initials: K
authors.lastname: Zolghadr
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Joseph
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Verma
authors.forename: David P
authors.initials: DP
authors.lastname: Lane
mesh_terms: D018797:Cell Cycle Proteins; D006801:Humans; D008958:Models, Molecular; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors / 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