INTRAMOLECULAR SEMIQUINONE DISPROPORTIONATION IN DNA - PULSE-RADIOLYSIS STUDY OF THE ONE-ELECTRON REDUCTION OF DAUNORUBICIN INTERCALATED IN DNA

被引:23
作者
HOUEELEVIN, C [1 ]
GARDESALBERT, M [1 ]
ROUSCILLES, A [1 ]
FERRADINI, C [1 ]
HICKEL, B [1 ]
机构
[1] CENS,CEA,CNRS,DSM,SCM,URA 331,F-91191 GIF SUR YVETTE,FRANCE
关键词
D O I
10.1021/bi00247a018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The One-electron reduction of daunorubicin, a quinonic antitumor antibiotic, intercalated in DNA was studied by pulse radiolysis using carboxyl radicals as reductants. The reaction's first stage is the daunorubicin semiquinone formation (k = 1.9 X 10(8) mol-1.dm3.s-1) in a way entirely consistent with a simple competition between .COO- disproportionation and the drug reduction. The semiquinone drug disappears by a first-order reaction (k = 1340 s-1) producing the hydroquinone form. This reaction leads to an equilibrium similar to the one without DNA and the equilibrium constant is very close to its value free in water (K(c) approximately 25). In addition, the stoichiometry of the first-order reaction is the one of a dismutation process. Therefore, it appears that the disproportionation occurs along an intramolecular path across DNA. This migration takes place under our experimental conditions, over a distance of ca. 100 base pairs, with a mobility of ca. 4.4 X 10(-11) m2.V-1.s-1, similar in magnitude to an excess electron mobility in doped organic polymers.
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页码:8216 / 8222
页数:7
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