8-Aza-7-deazapurine–pyrimidine base pairs: the contribution of 2- and 7-substituents to the stability of duplex DNA

Abstract

The 8-aza-7-deazapurin-2,6-diamine 2′-deoxyribonucleoside ( 2a )–dT base pair is more stable than the 2-amino-2′-deoxyadenosine ( 1 )–dT pair. Halogeno or propynyl substituents introduced in the 7-position of the 8-aza-7-deazapurine system ( 2b– d ) lead to an additional duplex stabilization. Pyrazolo[3,4- d]pyrimidine nucleosides related to 2′-deoxyadenosine or 2′-deoxyguanosine show a similar behavior. The base pair stabilization is comparably small when identical substituents are present in the 5-position of 2′-deoxyuridine. The extraordinary stability of the 2b– d –dT base pairs is caused by better proton donor properties of the two amino groups of the 8-aza-7-deazapurin-2,6-diamine moiety and the better base stacking induced by the 7-substituents compared to that of 2-aminoadenine.