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 (I)-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 nucteosides 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'-deoxyulidine. 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. (C) 2002 Elsevier Science Ltd. All rights reserved.