title: Universal Readers Based on Hydrogen Bonding or π-π Stacking for Identification of DNA Nucleotides in Electron Tunnel Junctions.
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 by1H 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.
authors.forename: Sovan
authors.initials: S
authors.lastname: Biswas
authors.forename: Suman
authors.initials: S
authors.lastname: Sen
authors.forename: JongOne
authors.initials: J
authors.lastname: Im
authors.forename: Sudipta
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Institute for Advanced Computational Science, Stony Brook University , Stony Brook, New York 11794-5250, United States.
authors.forename: Predrag
authors.initials: P
authors.lastname: Krstic
authors.forename: Brian
authors.initials: B
authors.lastname: Ashcroft
authors.forename: Chad
authors.initials: C
authors.lastname: Borges
authors.forename: Yanan
authors.identifier: 0000-0002-9909-5980
authors.initials: Y
authors.lastname: Zhao
authors.forename: Stuart
authors.initials: S
authors.lastname: Lindsay
authors.forename: Peiming
authors.identifier: 0000-0003-2831-2308
authors.initials: P
authors.lastname: Zhang
mesh_terms: D004247:DNA / Q000737:chemistry*; D004583:Electrons; D006860:Hydrogen Bonding; D006868:Hydrolysis; D009711:Nucleotides
chemical_list: D009711:Nucleotides; D004247:DNA
keywords: DNA sequencing; abasic site; hydrogen bonding; recognition tunneling; universal reader; π−π stacking