HOOGSTEEN-DUPLEX DNA - SYNTHESIS AND BASE-PAIRING OF OLIGONUCLEOTIDES CONTAINING 1-DEAZA-2'-DEOXYADENOSINE

Abstract

Oligodeoxyribonucleotides containing 1-deaza-2'-deoxyadenosine (= 7-amino-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3H-imidazo[4, 5-b]pyridine; 1b) form Hoogsteen duplexes. Watson-Crick base pairs cannot be built up due to the absence of N(1). For these studies, oligonucleotide building blocks - the phosphonate 3a and the phosphoramidite 3b - were prepared from 1b via 4a and 5, as well as the Fractosil-linked 6b, and used in solid-phase synthesis. The applicability of various N-protecting groups (see 4a-c) was also studied. The Hoogsteen duplex d[(c(1)A)(20].d(T?(20)) (11.13; T-m 15 degrees) is less stable than d(A(2)0).d(T-20) (12.13; T-m 60 degrees). The block oligomers d[(c(1)A)(10)-T-10] (14 and d[T-10-(c(1)A)(10] (15) containing purine and pyrimidine bases in the same strand are also able to form duplexes with each other. The chain polarity was found to be parallel.