Propynyl groups in duplex DNA: stability of base pairs incorporating 7-substituted 8-aza-7-deazapurines or 5-substituted pyrimidines

摘要

Oligonucleotides incorporating the 7-propynyl derivatives of 8-aza-7-deaza-2′-deoxyguanosine (>3b) and 8-aza-7-deaza-2′-deoxyadenosine (>4b) were synthesized and their duplex stability was compared with those containing the 5-propynyl derivatives of 2′-deoxycytidine (>1) and 2′-deoxyuridine (>2). For this purpose phosphoramidites of the 8-aza- 7-deazapurine (pyrazolo[3,4-d]pyrimidine) nucleosides were prepared and employed in solid-phase synthesis. All propynyl nucleosides exert a positive effect on the DNA duplex stability because of the increased polarizability of the nucleobase and the hydrophobic character of the propynyl group. The propynyl residues introduced into the 7-position of the 8-aza-7-deazapurines are generally more stabilizing than those at the 5-position of the pyrimidine bases. The duplex stabilization of the propynyl derivative >4b was higher than for the bromo nucleoside >4c. The extraordinary stability of duplexes containing the 7-propynyl derivative of 8-aza-7- deazapurin-2,6-diamine (>5b) is attributed to the formation of a third hydrogen bond, which is apparently not present in the base pair of the purin-2,6-diamine 2′-deoxyribonucleoside with dT.