Tautomeric equilibria of isoguanine and related purine analogs

ABSTRACT

Nucleobase pairs in DNA match hydrogen-bond donor and acceptor groups on the nucleobases. However, these can adopt more than one tautomeric form, and can consequently pair with nucleobases other than their canonical complements, possibly a source of natural mutation. These issues are now being re-visited by synthetic biologists increasing the number of replicable pairs in DNA by exploiting unnatural hydrogen bonding patterns, where tautomerism can also create mutation. Here, we combine spectroscopic measurements on methylated analogs of isoguanine tautomers and tautomeric mixtures with statistical analyses to a set of isoguanine analogs, the complement of isocytosine, the 5th and 6th “letters” in DNA.

KEYWORDS:

• Isoguanine
• isocytosine
• tautomer
• synthetic biology
• artificially expanded genetic information systems
• tautomeric ratios

Supporting information

¹H, ¹³C NMR, mass spectra for all the compounds are found in supporting information.

Acknowledgments

We are indebted for support from the Templeton World Charity Foundation [0092/AB57], NASA [NNX14AK37G], the National Science Foundation [MCB-1412869], and the Defense Threat Reduction Agency [HDTRA1-13-1-0004] for support of this work. We are indebted to Kevin M. Bradley for help preparing the figures containing spectra. We thank Dr. Theodore Martinot (Infinity Pharmaceuticals, Inc.) for his remarks on the analyses of UV spectra.