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 ener gy of interaction between the third strand and the double-stranded tar get, We tried to increase the stacking interaction contribution within the third strand by extending the aromatic domain of thymine, We repo rt here the use of 2,4-quinazolinedione as a substitute for thymine in the canonical TAT triplet, The synthesis and the characterization of the quinazoline beta nucleoside Q and of its phosphoramidite derivati ve is described, Triple-helix-forming oligonucleotides incorporating Q have been prepared and their ability to form triplexes has been evalu ated by UV-monitored thermal denaturation measurements, The introducti on of one or multiple Q residues, either contiguous or remote from eac h other, slightly destabilized triple-stranded structures, whatever th e nucleic acid base composition (pyrimidine or GT) of the third strand .