Quinazoline-2,4(1H,3H)-dione as a substitute for thymine in triple-helix forming oligonucleotides: a reassessment.
A major limitation in triple-helix formation arises from the weak energy of interaction between the third strand and the double-stranded target. We tried to increase the stacking interaction contribution within the third strand by extending the aromatic domain of thymine. We report here the use of 2,4-quinazolinedione as a substitute for thymine in the canonical TA*T triplet. The synthesis and the characterization of the quinazoline beta nucleoside Q and of its phosphoramidite derivative is described. Triple-helix- forming oligonucleotides incorporating Q have been prepared and their ability to form triplexes has been evaluated by UV-monitored thermal denaturation measurements. The introduction of one or multiple Q residues, either contiguous or remote from each other, slightly destabilized triple-stranded structures, whatever the nucleic acid base composition (pyrimidine or GT) of the third strand.
Michel
J
J
INSERM U-386, Laboratoire de Biophysique Moléculaire, Université de Bordeaux, France.
Toulmé
J J
JJ
Vercauteren
J
J
Moreau
S
S
D004355:Drug Stability; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D011799:Quinazolines / Q000138:chemical synthesis / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry*
D009841:Oligonucleotides; D011799:Quinazolines; C081989:2,4(1H,3H)-quinazolinedione; D013941:Thymine