Département de chimie moléculaire

The photo-triggered cleavage of chem. bonds has found numerous applications in biol., particularly in the field of gene sequencing through photo-induced DNA strand scission. However, only a small no. of modified nucleosides that are able to cleave DNA at selected positions have been reported in the literature. Herein, we show that a new photo-activable deoxyadenosine analog, 3-nitro-3-deaza-2'-deoxyadenosine (d(3-NiA)), was able to induce DNA backbone breakage upon irradn. ($łambda$ {\textgreater} 320 nm). The d(3-NiA) nucleoside was chem. incorporated at desired positions into 40-mer oligonucleotides as a phosphoramidite monomer and subsequent hybridization studies confirmed that the resulting modified duplexes display a behavior that is close to that of the related natural sequence. Enzymic action of the Klenow fragment exonuclease free revealed the preferential incorporation of dAMP opposite the 3-NiA base. On the other hand, incorporation of the analogous 3-NiA triphosphate to a primer revealed high enzyme efficiency and selectivity for insertion opposite thymine. Furthermore, only the enzymically synthesized base pair 3-NiA:T was a substrate for further extension by the enzyme. All the hybridization and enzymic data indicate that this new photo-activable 3-NiA triphosphate can be considered as a photochem. cleavable dATP analog. [on SciFinder(R)]