9-[(10-(aden-9-yl)-4,8-diazadecyl)amino]-6-chloro-2-methoxy-acridine incises DNA at apurinic sites.
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 molecule 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 beta-elimination.
Constant
J F
JF
LEDSS (UA CNRS 332), Chimie Recherche, Université Scientifique et Médicale de Grenoble, Saint-Martin d'Heres, France.
O'Connor
T R
TR
Lhomme
J
J
Laval
J
J
D000166:Acridines; D000609:Aminoacridines; D001080:Apurinic Acid; D002384:Catalysis; D004256:DNA Polymerase I / Q000378:metabolism; D004278:DNA, Superhelical; D004305:Dose-Response Relationship, Drug; D006868:Hydrolysis; D007700:Kinetics; D010084:Oxidation-Reduction; D010957:Plasmids; D011119:Polynucleotides; D013329:Structure-Activity Relationship
C055678:2-chloro-6-methoxy-2-((adenyl-9)-11)-4,8-diazadecylamino-9-acridine; D000166:Acridines; D000609:Aminoacridines; D004278:DNA, Superhelical; D011119:Polynucleotides; D001080:Apurinic Acid; D004256:DNA Polymerase I