Sources of hydrogen abstraction by activated neocarzinostatin chromophore

• Published in: Biochemistry (Easton) Vol. 32; no. 14; pp. 3611 - 3616
• Main Authors: Chin, Der Hang, Goldberg, Irving H
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 13.04.1993
• Subjects: Biological and medical sciences; Chromatography, High Pressure Liquid; Deuterium; DNA Damage; Enediynes; General pharmacology; Glutathione - pharmacology; Hydrogen - chemistry; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Structure; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Solvents; Stereoisomerism; Sulfhydryl Compounds - pharmacology; Zinostatin - analogs & derivatives; Zinostatin - chemistry; Zinostatin - pharmacology; Antineoplastic agent; Reaction mechanism; Cytotoxicity; Antibiotic; Radiolabelling; Diastereomer

Activation of the enediyne neocarzinostatin chromophore (NCS-Chrom) by thiol addition at C-12 generates a diradical species with radical centers at C-2 and C-6, which abstract hydrogens from deoxyribose in the minor groove of DNA. Since hydrogen abstraction from DNA accounts for only part of the hyd...