Synthesis and characterization of oligodeoxynucleotides containing a novel tetraazabenzo[cd]azulene:naphthyridine base pair

Abstract

The synthesis and thermal stability of oligodeoxynucleotides (ODNs) containing 4-amino-2,3,5,6-tetraazabenzo[cd]azulen-7-one nucleosides 5 (BaO(N)) with the aim of developing new base pairing motif is described. The tricyclic nucleoside 5 was prepared starting with the 7-deaza-7-iodopurine derivative 1 via a palladium catalyzed cross-coupling reaction with methyl acrylate, followed by an intramolecular cyclization. The resulting nucleoside was incorporated into ODNs, and the base pairing property of the BaO(N):NaN(O) (2-amino-7-hydroxy-1,8-naphthyridine nucleoside) pair in the duplex was evaluated by a thermal denaturation study. The melting temperature (T(m)) of the duplex containing the BaO(N):NaN(O) pair showed a higher value than that of the duplexes containing the adenine:thymine (A:T) and the guanine:cytosine (G:C) pairs, however it was lower than that of the ImO(N):NaN(O) (ImO(N)=7-amino-imidazo[5',4':4,5]pyrido[2,3-d]pyrimidin-4(5H)-one nucleoside) pair. A temperature-dependent (1)H NMR study revealed that the H-bonding ability of BaO(N) was lower than that of ImO(N), which would explain why the BaO(N):NaN(O) pair was less thermally stable than the ImO(N):NaN(O) pair.