DUPLEX STABILIZATION OF DNA - OLIGONUCLEOTIDES CONTAINING 7-SUBSTITUTED 7-DEAZAADENINES

The oligonucleotide building blocks 4b-d derived from 7-bromo-, 7-chloro-, and 7-methyl-substituted 7-deaza-2'-deoxyadenosines 3b-d were prepared. They were employed in the solid-phase synthesis of the oligonucleotides 7-25. The dA residues of the homomer d(A(12)), the alternating d[(A-T)(6)], and the palindromic d(G-T-A-G-A-A-T-T-C-T-A-C) were replaced by 3b-d as well as by the parent 7-deaza-2'-deoxyadenosine (3a). The melting profiles and CD spectra of oligonucleotide duplexes, showing this major groove modification, were measured, and the T-m values as well as the thermodynamic data were determined. It was found that small substituents such as Br, Cl, or Me introduced in the 7-position of a 7-deazaadenine residue increase the duplex stability compared to oligonucleotides containing adenine.