Spontaneous generation of a biradical species of neocarzinostatin chromophore: role in DNA bulge-specific cleavage.
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.
Hensens
O D
OD
Natural Products Chemistry Department, Merck Research Laboratories, Rahway, NJ 07065.
Chin
D H
DH
Stassinopoulos
A
A
Zink
D L
DL
Kappen
L S
LS
Goldberg
I H
IH
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*
D004247:DNA; D009353:Zinostatin