Analogues of P and Z as Efficient Artificially Expanded Genetic Information System.

To artificially expand the genetic information system and to realize artificial life, it is necessary to discover new functional DNA bases that can form stable duplex DNA and participate in error-free replication. It is recently proposed that the 2-amino-imidazo[1,2- a]-1,3,5-triazin-4(8 H)one (P) and 6-amino-5-nitro-2(1 H)-pyridone (Z) would form a base pair complex, which is more stable than that of the normal G-C base pair and would produce an unperturbed duplex DNA. Here, by using quantum chemical calculations in aqueous medium, it is shown that the P and Z molecules can be modified with the help of electron-withdrawing and -donating substituents mainly found in B-DNA to generate new bases that can produce even more stable base pairs. Among the various bases studied, P3, P4, Z3, and Z5 are found to produce base pairs, which are about 2-15 kcal/mol more stable than the P-Z base pair. It is further shown that these base pairs can be stacked onto the G-C and A-T base pairs to produce stable dimers. The consecutive stacking of these base pairs is found to yield even more stable dimers. The influence of charge penetration effects and backbone atoms in stabilizing these dimers are also discussed. It is thus proposed that the P3, P4, Z3, and Z5 would form promiscuous artificial genetic information system and can be used for different biological applications. However, the evaluations of the dynamical effects of these bases in DNA-containing several nucleotides and the efficacy of DNA polymerases to replicate these bases would provide more insights.