Universal readers based on hydrogen bonding or <script type="math/tex">\pi-\pi</script> stacking for identification of DNA nucleotides in electron tunnel junctions

Biswas, Sovan; Sen, Suman; Im, JongOne; Biswas, Sudipta; Krstic, Predrag; Ashcroft, Brian; Borges, Brian; Zhao, Yanan; Lindsay, Stuart; Zhang, Peiming

doi:10.1021/ACSNANO.6B06466

Title

Universal readers based on hydrogen bonding or $\pi-\pi$ stacking for identification of DNA nucleotides in electron tunnel junctions

Author

Biswas, Sovan

Sen, Suman

Im, JongOne

Biswas, Sudipta

Krstic, Predrag

Ashcroft, Brian

Borges, Brian

Zhao, Yanan

Lindsay, Stuart

Zhang, Peiming

Abstract

A reader molecule, which recognizes all the naturally occurring nucleobases in an electron tunnel junction, is required for sequencing DNA by a recognition tunneling (RT) technique, referred to as a universal reader. In the present study, we have designed a series of heterocyclic carboxamides based on hydrogen bonding and a large-sized pyrene ring based on a π–π stacking interaction as universal reader candidates. Each of these compounds was synthesized to bear a thiolated linker for attachment to metal electrodes and examined for their interactions with naturally occurring DNA nucleosides and nucleotides by 1H NMR, ESI-MS, computational calculations, and surface plasmon resonance. RT measurements were carried out in a scanning tunnel microscope. All of these molecules generated electrical signals with DNA nucleotides in tunneling junctions under physiological conditions (phosphate buffered aqueous solution, pH 7.4). Using a support vector machine as a tool for data analysis, we found that these candidates distinguished among naturally occurring DNA nucleotides with the accuracy of pyrene (by π–π stacking interactions) > azole carboxamides (by hydrogen-bonding interactions). In addition, the pyrene reader operated efficiently in a larger tunnel junction. However, the azole carboxamide could read abasic (AP) monophosphate, a product from spontaneous base hydrolysis or an intermediate of base excision repair. Thus, we envision that sequencing DNA using both π–π stacking and hydrogen-bonding-based universal readers in parallel should generate more comprehensive genome sequences than sequencing based on either reader molecule alone.

Language

English

Source (journal)

ACS nano. - -

Publication

2016

ISSN

1936-0851

DOI

10.1021/ACSNANO.6B06466

Volume/pages

10 :12 (2016) , p. 11304-11316