Synthesis of 1,8-Naphthyridine C-Nucleosides and Their Base-Pairing Properties in Oligodeoxynucleotides: Thermally Stable Naphthyridine:Imidazopyridopyrimidine Base-Pairing Motifs

摘要

A number of nucleoside analogues that contain non-natural nucleobases have been synthesized and incorporated into oligodeoxynucleotides (ODNs) with the aim of biological, bioengineering, and therapeutic applications.[1], [2] The development of new base-pairing motifs beyond the Watson-Crick hydrogen bonding (H bonding) model for thermal stability and specificity is therefore still an area of active research.[3], [4] We recently reported the synthesis of imidazo[5,4:4,5]pyrido[2,3-d]pyrimidine nucleosides with the ability to form four H bonds and discussed their hybridization properties in ODNs (Scheme 1 A).[5], [6] Accordingly, the Im-N~O:Im-O~N base pair markedly stabilized a duplex when three of the pairs were consecutively incorporated into ODNs. However, incorporation of one pair into ODNs resulted in destabilization of the duplex relative to those containing A:T and G:C base pairs. These results were explained by the conflicting effects of the Im-NO:Im-ON pair in ODNs, that is, the pair stabilizes the duplex with four H bonds, but it widens of the helix because the C1-C1 distance is longer than that in the Watson-Crick base pair - a destabilizing factor for the duplex that contains the pair.