title: Achieving cell penetration with distance-matching cysteine cross-linkers: a facile route to cell-permeable peptide dual inhibitors of Mdm2/Mdmx.
abstract: We report the design of bisarylmethylene bromides as a new class of rigid, distance-matching cysteine cross-linkers. By cross-linking a peptide dual inhibitor of Mdm2/Mdmx containing cysteines at i,i+7 positions, dramatic enhancement in cell permeability was achieved, along with increased helicity and biological activity.
authors.affiliation: Department of Chemistry, State University of New York at Buffalo, Buffalo, New York 14260, USA.
authors.forename: Avinash
authors.initials: A
authors.lastname: Muppidi
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Wang
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; D002463:Cell Membrane Permeability; D003545:Cysteine / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; 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
chemical_list: D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D003545:Cysteine