OLIGODEOXYRIBONUCLEOTIDES CONTAINING 4-AMINOBENZIMIDAZOLE IN-PLACE OF ADENINE - SOLID-PHASE SYNTHESIS AND BASE-PAIRING

Abstract

Oligonucleotides containing 4-aminobenzimidazole 2'-deoxyribofuranoside (1,3-dideaza-2'-deoxyadenosine; c(1)c(3)A(d), 1) were synthesized. For this purpose, various NH2-protecting groups were investigated, and the [(9H-fluoren-9-yl)methoxy]carbonyl group was selected for phosphoramidite protection (--> 4c). Apart from the phosphoramidite 3, the phosphonate 2 was prepared. Compound 1 was incorporated in a homooligonucleotide as well as in oligomers containing naturally occurring nucleosides. The T-m values and the thermodynamic data of various duplexes (11.10, 17.10, 18.10) containing 4-aminobenzimidazole were determined. Although d[(c(1)c(3)A)(20)] (11) does not form a Hoogsteen duplex with d(T-20) (10) as observed with d[(c(1)A)(20)], it destabilizes the Watson-Crick duplexes to a much smaller extent than it was expected from a bulged loop structure. Apparently, 4-aminobenzimidazole interacts with regular nucleoside residues within a Watson-Crick duplex structure, most likely by vertical stacking. According to the low basicity of the amino group, only weak H-bonding is expected.