title: Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition.
abstract: We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity.
authors.affiliation: Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Madden
authors.forename: Avinash
authors.initials: A
authors.lastname: Muppidi
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Li
authors.forename: Jiandong
authors.initials: J
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D003500:Cyclization; D004797:Enzyme-Linked Immunosorbent Assay; D020128:Inhibitory Concentration 50; D008027:Light; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors*
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2