THEORETICAL AND EXPERIMENTAL-STUDY OF ISOGUANINE AND ISOCYTOSINE - BASE-PAIRING IN AN EXPANDED GENETIC SYSTEM

The stabilities of all possible purine/pyrimidine pairings between the isomeric nucleobases isocytosine (iso-C) and isoguanine (iso-G) and s tandard genomic bases are reported for two independent oligonucleotide duplexes. Additionally, results are given from ab initio calculations performed on iso-C and iso-G. The calculations are used as an aid in the interpretation of thermodynamic data obtained from duplex denatura tion studies. The unnatural iso-C/iso-G pair is found to be as stable as a C/G Watson-Crick pair in both duplex systems. The next most stabl e unnatural pair is that formed by C/iso-G and is observed to be isoen ergetic with a U/A Watson-Crick Fair. Ab initio data suggest iso-G may adopt an unprecedented imino oxo tautomer which could explain the unu sual stability of the C/iso-G pair. The stability of the other possibl e unnatural pairs are reported and similarly interpreted in terms of a b initio and other available experimental data. Finally, the fitness i s discussed of a six-component genetic system that includes iso-C, iso -G, and four standard genomic bases.