Synthesis of Thymidine Dimers Containing Piperazine in the Internucleoside Linkage and their Incorporation into Oligodeoxynucleotides

Article abstract of DOI:10.1016/0040-4020(94)01088-H

The synthesis of thymidine dimers in which the natural phosphodiester linkage has been replaced by piperazine (3'-(N(CH2CH2)2N)-5, 9 and 3'-(N(CH2CH2)2N)-CO-4, 10) are described.These new dimers were incorporated into oligodeoxynucleotides on an automated DNA-synthesizer using the phosphoramidite approach.The thermal stability of DNA/DNA duplexes and the enzymatic stability was studied by UV experiments. 17-Mers with 9 incorporated once or twice in the middle exhibited a pronounced decrease in thermal stability (ΔT_m -11 degC per modification) while 17-mers with 10 incorporated once or twice in the middle exhibited only a slight decrease in thermal stability (ΔT_m -2 degC per modification) when compared to unmodified 17-mers.Furthermore, end-modified oligodeoxynucleotides containing either 9 or 10 displayed five to six fold increased stability towards snake venom phosphodiesterase.