1367204-11-2Relevant academic research and scientific papers
Synthesis of C8-Arylamine-Modified 2′-Deoxyadenosine Phosphoramidites and their Site-Specific Incorporation into Oligonucleotides
Szombati, Zita,Baerns, Sabrina,Marx, Andreas,Meier, Chris
, p. 700 - 712 (2012/06/04)
Adducts of C8-(N-acetyl)-arylamines and 2′-deoxyadenosine were synthesised by palladium-catalysed C-N cross-coupling chemistry. These 2′-dA adducts were converted into the corresponding 3′-phosphoramidites and site-specifically incorporated into DNA oligonucleotides, which were characterised by mass spectrometry, UV thermal-stability assays and circular dichroism. These modified oligonucleotides were also used in EcoRI restriction assays and in primer-extension studies with three different DNA polymerases. The incorporation of the 2′-dA lesion close to the EcoRI restriction site dramatically reduced the susceptibility of the DNA strand to cleavage; this indicates a significant local distortion of the DNA double helix. The incorporation of the acetylated C8-2′-dA-phosphoramidites into 20-mer oligonucleotides failed, however, because the N-acetyl group was lost during the deprotection process. Instead the corresponding C8-NH-2′-dA-modified oligonucleotides were obtained. The effect of the C8-NH-arylamine-dA lesion on the replication by DNA polymerases was clearly dependent both on the polymerase used and on the arylamine-dA damage.
