The new imidazopyridopyrimidine:naphthyridine basepairing motifs, ImO O :NaN N and ImN N :NaO O , were designed. Among the base pairs examined, DNA duplexes containing 10 ImN N :NaO O pair(s) consisting of a DAAD:ADDA hydrogen bonding pattern (D = donor, A = acceptor) were markedly stabilized thermally and thermodynamically. Hydrogen bonding (H-bonding) is one of the most important nonbonded molecular interactions. Therefore, it is important to 15 understand the molecular recognition process in

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... biology and in the design of functional organic supramolecules through Hbonding. In the field of nucleic acid chemistry, for example, specific H-bonding between adenine and thymine (A:T) and guanine and cytosine (G:C), the Watson-Crick base pairs, plays a 20 critical role not only in conserving and transmitting genetic information but also in duplex stability. Furthermore, the development of an artificial base-pairing motif beyond the Watson-Crick base pairs is an area of active research with the aim of expanding biological, bioengineering, and therapeutic 25 applications. 1-3 Figure 1. Imidazopyridopyrimidine:naphthyridine (Im:Na) base-pairing motifs consisting of four H-bonds. A) ImO N :NaN O , B) ImN O :NaO N , C) ImO O :NaN N , and D) ImN N :NaO O 30 We have been working on a project to develop new base-pairing motifs consisting of four hydrogen bonds (H-bonds) designed to stabilize and regulate DNA structure. 4-7 We have already prepared two sets of base-pairing motifs consisting of the imidazopyridopyrimidine:naphthyridine (Im:Na) pairs, that is, the 35 ImO N :NaN O and ImN O :NaO N pairs shown in Figure 1A and B. 4,5 Since the resulting base-pairing motifs were specific and markedly stabilized DNA duplexes (ca. +8 °C per pair relative to an A:T pair) independent of the sequence context, we attempted to develop thermally stabilized decoy molecules. 8 Furthermore, 40 we have recently demonstrated the selective recognition of ImO N :NaN O and ImN O :NaO N pairs by DNA polymerases. 9.10 These successful results prompted us to develop new base-pairing motifs consisting of a series of Im:Na pairs. As can be seen in Figure 1A and B, the previous ImO N :NaN O and ImN O :NaO N pairs 45 have alternate H-bonding patterns of ADAD:DADA and DADA:ADAD, respectively (A = acceptor, D = donor). Since it has been suggested that the stability of hydrogen bonded complexes is affected by the arrangement of H-bonds arising from a secondary interaction, 11 we designed new base-pairing 50 motifs, the ImO O :NaN N and ImN N :NaO O pairs ( Figure 1C and D), that possess ADDA:DAAD and DAAD:ADDA H-bonding patterns, which are expected to be more stable than the alternate H-bonding patterns. In this communication, we report the synthesis of the new 55 naphthyridine derivatives, NaN N and NaO O , and their basepairing property with ImO O and ImN N , 4 respectively. The basepairing property of ImO O :NaN N was almost equal to those of the ImO N :NaN O and ImN O :NaO N pairs. In contrast, the ImN N :NaO O pair thermally and thermodynamically stabilized its duplex more 60 than the ImO N :NaN O and ImN O :NaO N pairs. These results are also discussed. The desired NaN N and NaO O (5 and 10) were prepared from the NaO N derivative 1 5 (Scheme 1). Thus, the 3' and 5'-hydroxyl groups of 1 were protected by acetyl groups to give 2. In order to 65 convert the 7-oxo group of 2 into an amino group, 2 was treated with POCl 3 at room temperature to give the 7-chloro derivative 3 in 85% yield. The resulting 3 was treated with NH 3 in MeOH at 80 °C to afford the free nucleoside 4. Since the 7-chloro group was inactive under the above conditions, 4 was treated with liq. 70 NH 3 at 120 °C to give the desired NaN N (5) in 88% yield.