Oligonucleotides containing pyrazolo[,4-d]pyrimidines: The influence of 7-substituted 8-aza-7-deaza-2 '-deoxyguanosines on the duplex structure and stability

Oligonucleotides containing 7-substituted 8-aza-7-deazaguanines (= 6-amino- 1,5-dihydro-4H-pyrazolo[3.4-d]pyrimidin-4-ones) were prepared by automated solid-phase synthesis. A series of 7-alkynylated 8-aza-7-deaza-2'-deoxyguan osines (see 4a-d)were synthesized with the 7-iodonucleoside 3c as starting material and by the Pd-0/Cu-I-catalyzed cross-coupling reaction with variou s alkynes. Phosphoramidites were prepared from the 7-substituted 8-aza-7-de aza-2'-deoxyguanosine derivatives carrying halogeno, cyano, and hexynyl sub stituents. From the melting profiles of oligonucleotide duplexes. the T-m v alues as well as the thermodynamic data were determined. A significant dupl ex stabilization by the 7-substituents was observed for the DNA . DNA duple xes, but not in the case of DNA . RNA hybrids.