title: Selective proteolytic activity of the antitumor agent kedarcidin.
abstract: Kedarcidin is a potent antitumor antibiotic chromoprotein, composed of an enediyne-containing chromophore embedded in a highly acidic single chain polypeptide. The chromophore was shown to cleave duplex DNA site-specifically in a single-stranded manner. Herein, we report that in vitro, the kedarcidin apoprotein, which lacks any detectable chromophore, cleaves proteins selectively. Histones that are the most opposite in net charge to the apoprotein are cleaved most readily. Our findings imply that the potency of kedarcidin results from the combination of a DNA damaging-chromophore and a protease-like apoprotein.
authors.affiliation: Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
authors.forename: N
authors.initials: N
authors.lastname: Zein
authors.forename: A M
authors.initials: AM
authors.lastname: Casazza
authors.forename: T W
authors.initials: TW
authors.lastname: Doyle
authors.forename: J E
authors.initials: JE
authors.lastname: Leet
authors.forename: D R
authors.initials: DR
authors.lastname: Schroeder
authors.forename: W
authors.initials: W
authors.lastname: Solomon
authors.forename: S G
authors.initials: SG
authors.lastname: Nadler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D001059:Apoproteins / Q000302:isolation & purification / Q000378:metabolism*; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D006657:Histones / Q000302:isolation & purification / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007700:Kinetics; D008969:Molecular Sequence Data; D010455:Peptides; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism; D013379:Substrate Specificity; D009353:Zinostatin / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D001059:Apoproteins; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011506:Proteins; C069636:kedarcidin peptide; D009353:Zinostatin; D010450:Endopeptidases