title: Spontaneous generation of a biradical species of neocarzinostatin chromophore: role in DNA bulge-specific cleavage.
abstract: Detailed structure determination of the major and minor base-catalyzed degradation products of the chromophore of the enediyne anticancer antibiotic neocarzinostatin in the absence of DNA demonstrates that the enolate Michael addition reaction leading to a spirolactone cumulene intermediate is a spontaneous, stereoselective process. The implications of these findings for the mechanism of the thiol-independent, site-specific cleavage by the so-generated radical species of the drug at a DNA bulge are described.
authors.affiliation: Natural Products Chemistry Department, Merck Research Laboratories, Rahway, NJ 07065.
authors.forename: O D
authors.initials: OD
authors.lastname: Hensens
authors.forename: D H
authors.initials: DH
authors.lastname: Chin
authors.forename: A
authors.initials: A
authors.lastname: Stassinopoulos
authors.forename: D L
authors.initials: DL
authors.lastname: Zink
authors.forename: L S
authors.initials: LS
authors.lastname: Kappen
authors.forename: I H
authors.initials: IH
authors.lastname: Goldberg
mesh_terms: D004247:DNA / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008968:Molecular Conformation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D016339:Spectrometry, Mass, Fast Atom Bombardment; D009353:Zinostatin / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D004247:DNA; D009353:Zinostatin