ChemInform Abstract: Synthesis, Base Pairing, and Structural Transitions of Oligodeoxyribonucleotides Containing 8-Aza-2′-deoxyguanosine.

Abstract

The synthesis of oligonucleotides containing 8-aza-2′-deoxyguanosine (z8Gd; 1) or its N8-regioisomer z8Gd* (2) instead of 2′-deoxyguanosine (Gd) is described. For this purpose, the NH2 group of 1 and 2 was protected with a (dimethylamino)methylidene residue (5, 6), a 4,4′-dimethoxytrityl group was introduced at 5′-OH ( 7, 8), and the phosphonates 3a and 4 as well as the phosphoramidite 3b were prepared. These building blocks were used in solid-phase oligonucleotide synthesis. The oligonucleotides were characterized by enzymatic hydrolysis and melting curves (Tm values). The thermodynamic data of the oligomers 12–15 indicate that duplexes were stabilized when 1 was replacing Gd. The aggregation of d(T-G-G-G-G-T) (18) was studied by RP 18 HPLC, gel electrophoresis and CD spectroscopy and compared with that of oligonucleotides containing an increasing number of z8Gd residues instead of Gd. Similarly to [d(C-G)]3 (12a), the hexamer d(C-z8G-C-z8G-C-G) (14) underwent salt-dependent B-Z transition.