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Nucleic Acids Research, 1988, Vol. 16, No. 6 2691-2703
© 1988

Articles

9-[(10-(aden-9-yl)-4,8-diazadecyl)amino]-6-chloro-2-methoxy-acridine incises DNA at apurinic sites

J.F. Constant, T.R. O'Connor1, J. Lhomme and J. Laval1,*

LEDSS (UA CNRS 332), Chimie Recherche, Université Scientifique et Médicale de Grenoble BP 68, 38402 Saint-Martin d'Heres, France 1Groupe Reparation des Lésions Radio et Chimio Induites, UA 147 CNRS and U 140 INSERM, Institut Gustave Roussy 94805 Villejuif Cédex, France

*To whom correspondance should be address

Received November 25, 1987. Revised February 19, 1988. Accepted February 19, 1988.

The incision of DNA at apurinic/apyrimidinic sites (AP-sites) by chloro-6-methoxy-2 ((adenyl-9)-11–4,8 diazadecyl )amino-9 acridine (Ade-Z-Acr), a 9-aminoacridine linked to an adenine, at nanomolar concentrations is described. Moreover, this drug, Ade-Z-Acr, is one of the most efficient drugs which cleaves DNA at AP-sites. The high activity is the result of the composition of the drug, since the individual components have no incising activity in the concentration range studied. The termini left by the Ade-Z-Acr mole cule are a 3'deoxyribose and a 5'nucleotide. The termini and the inability of the Ade-Z-Acr to incise DNA with reduced AP-sites suggest that the mechanism of cleavage is u-elimination.


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