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.