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Spectroscopic studies of neocarzinostatin and its chromophore: UV inactivation and mercaptan activation
Author(s) -
Sheridan Robert P.,
Gupta Raj K.
Publication year - 1981
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560200730
Subject(s) - neocarzinostatin , chromophore , chemistry , photochemistry , radical , dna , electron paramagnetic resonance , enediyne , ultraviolet light , fluorescence , ultraviolet , stereochemistry , organic chemistry , biochemistry , nuclear magnetic resonance , physics , quantum mechanics
Neocarzinostatin, an antitumor protein antibiotic containing an essential nonprotein chromophore, causes single‐strand breaks in DNA in vitro. Mercaptans are required for the DNA‐cleavage activity, and irradiation of the protein by ultraviolet light destroys this activity. Observations are reported from optical, fluorescence, EPR, and 1 H NMR spectroscopy on the irreversible changes induced in neocarzinostatin, and where possible in the isolated chromophore, by ultraviolet irradiation and treatment with mercaptans. For the first time it was found that EPR‐detectable short‐lived chromophore‐dependent radicals are formed during ultraviolet inactivation and mercaptan activation of neocarzinostatin. Mercaptan‐induced chromophoric radicals detected in this study may participate in DNA cleavage, but decay unproductively in the absence of DNA. 1 H NMR and fluorescence results are consistent with the idea that dissociation of the chromophore from aromatic groups in the protein accompanies inactivation and activation. Both inactivation and activation of the drug involve substantial changes in the structure of the chromophore.