Highly Conductive Nucleotide Analogue Facilitates Base-Calling in Quantum-Tunneling-Based DNA Sequencing

Quantum tunneling-based DNA sequencing is a single molecular technology that has a great potential for achieving facile and high throughput DNA sequencing. In principle, sequence of DNA could be read out by the time trace of tunnel current that can be changed according to molecular conductance of nucleobases passing through nano-sized gap electrodes. However, efficient base-calling of four genetic alphabets has been seriously impeded due to the similarity of molecular conductance among canonical nucleotides. In this article, we demonstrated that replacement of canonical 2’-deoxyadenosine (dA) with a highly conductive dA analog, 7-deaza dA could expand the difference of molecular conductance between four genetic alphabets. Additionally, systematic evaluation of molecular conductance using a series of dA and dG analogues revealed that molecular conductance of the nucleotide is highly dependent on the HOMO level. Thus, the present study demonstrating signal characteristics of the nucleotide can be modulated ...