Synthesis of thymidine dimers containing piperazine in the internucleoside linkage and their incorporation into oligodeoxynucleotides

• Published in: Tetrahedron Vol. 51; no. 7; pp. 2145 - 2154
• Main Authors: Petersen, Gorm Vang, Wengel, Jesper
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 13.02.1995; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; LINKED DINUCLEOSIDES; SOLID-PHASE SYNTHESIS; ANALOGS; BUILDING-BLOCKS; 3'-AMINO-3'-DEOXYTHYMIDINE; OLIGODEOXYRIBONUCLEOTIDES; ANTISENSE OLIGONUCLEOTIDES; DERIVATIVES; HYBRIDIZATION PROPERTIES; FORMACETAL
• ISSN: 0040-4020; 1464-5416
• 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The synthesis of thymidine dimers in which the natural phosphodiester linkage has been replaced by piperazine (3′-(N(CH 2CH 2) 2N)-5′, 9 and 3′-(N(CH 2CH 2) 2N)-CO-4′, 10) are described.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 °C 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 δC 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. The synthesis of new diamine linked thymidine dimers have been accomplished. The thermal and enzymatic stability of oligodeoxynucleotides containing these dimers have been evaluated.