The ability of a triplex-forming oligonucleotide to recognize T-A and C-G base pairs in a DNA duplex is enhanced by incorporating N-acetyl-2,7-diaminoquinoline.

A triplex-forming oligonucleotide (TFO) can recognize the homopurine-homopyrimidine sequence in DNA duplexes and inhibit the transcription of targeted mRNAs. Recently, we reported that N-acetyl-2,7-diamino-1,8-naphthyridine (N), incorporated into a TFO, has high binding ability and base recognition selectivity for the pyrimidine bases in the purine-rich chain of the DNA duplex at pH 7.4. However, it was found in this study that the difference in the T values between the pyrimidine bases and purine bases decreased by more than 4 °C at pH 6.0-7.0. To improve the low base recognition selectivity of the TFO, we designed a new artificial base, Q, with a quinoline skeleton. The T values of the triplexes containing Q:T-A or Q:C-G were more than 13 °C higher than those of the triplexes containing Q:A-T or Q:G-C at pH 7.4. We also observed that under more acidic conditions (pH 6.0-7.0), the base recognition selectivity of Q in a triplex was higher than that of N, although the binding ability of Q in a triplex was similar to that of N. Additionally, we found that Q, incorporated into the TFO, could accurately recognize the C-G base pair in the hairpin DNA, similar to the C-G base pair.