Low concentrations of acridine dimers inhibit micrococcus AP endonuclease through interaction with apurinic sites in DNA.
The effect of dimeric DNA intercalating compounds was assayed on a purified AP endonuclease from Microccoccus luteus using apurinic supercoiled PM2 DNA as a substrate. Binding on apurinic sites was estimated through the competition with the intercalating compound, 9-NH2-ellipticine, which displays great specificity for apurinic sites. An acridine dimer with a spermine linker is at 0.1 microM the best inhibitor of cleavage at the apurinic site induced either by the AP endonuclease or by 9-NH2-ellipticine. Bisintercalating agents are more effective inhibitors of AP endonuclease than monointercalating ones. Most effective inhibitors among dimers have acridine residues.
URA 158 CNRS, U-140 INSERM, Institut G. Roussy, Villejuif, France.
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C
Malvy
J
J
Pierre
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Lefrançois
J
J
Markovits
C
C
Garbay
B
B
Roques
D000166:Acridines / Q000494:pharmacology*; D001080:Apurinic Acid / Q000378:metabolism*; D001665:Binding Sites; D001667:Binding, Competitive; D004278:DNA, Superhelical / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004611:Ellipticines / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000037:antagonists & inhibitors*; D006358:Hot Temperature; D007364:Intercalating Agents; D008837:Micrococcus / Q000201:enzymology*; D015394:Molecular Structure; D011119:Polynucleotides / Q000378:metabolism*
D000166:Acridines; D004278:DNA, Superhelical; D004611:Ellipticines; D007364:Intercalating Agents; D011119:Polynucleotides; D001080:Apurinic Acid; C038373:9-aminoellipticine; D004706:Endodeoxyribonucleases; D043223:Deoxyribonuclease IV (Phage T4-Induced); D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase