Synthesis, thermal stability and reactivity towards 9-aminoellipticine of double-stranded oligonucleotides containing a true abasic site.
A 13 mers abasic oligonucleotide was synthetized. It was therefore possible to compare thermal stability and reactivity of duplex oligonucleotides either with an apurinic/apyrimidinic site or without any lesion. An important decrease in the melting temperature appeared for duplexes with an abasic site. The chemical reaction of these modified oligonucleotides with the intercalating agent 9-aminoellipticine was studied by gel electrophoresis and by fluorescence. The formation of a Schiff base between 9-aminoellipticine and abasic sites was rapid and complete with duplexes at 11 degrees C. Schiff base related fluorescence and beta-elimination cleavage were more important with the apyrimidinic sites than with the apurinic ones. When compared to previous results obtained with the model d(TprpT) some unexpected behaviours appeared with longer and duplex oligonucleotides. For instance only partial beta-elimination cleavage was observed. It is likely that stacking parameters in the double helix play a great role in the studied reaction.
Bertrand
J R
JR
Laboratoire de Biochimie-Enzymologie, UA 147 CNRS, UA 140 INSERM, Institut Gustave-Roussy, Villejuif, France.
Vasseur
J J
JJ
Rayner
B
B
Imbach
J L
JL
Paoletti
J
J
Paoletti
C
C
Malvy
C
C
D000470:Alkaloids; D001080:Apurinic Acid; D001483:Base Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D004611:Ellipticines; D006358:Hot Temperature; D007364:Intercalating Agents; D007700:Kinetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011089:Polydeoxyribonucleotides / Q000138:chemical synthesis; D011119:Polynucleotides; D012545:Schiff Bases; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship
D000470:Alkaloids; D004611:Ellipticines; D007364:Intercalating Agents; D011089:Polydeoxyribonucleotides; D011119:Polynucleotides; D012545:Schiff Bases; C001790:apyrimidinic acid; D001080:Apurinic Acid; C038373:9-aminoellipticine