A Novel Method of Labelling DNA Bases for Sequencing

An international research team headed by Michal Hocek of the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague) and Charles University and Ciara K. O’Sullivan of Universitat Rovira i Virgili (URV) in Spain have developed a novel method for labelling DNA, which in the future can be used for sequencing DNA by means of electrochemical detection. The researchers presented their results in the Journal of the American Chemical Society.

A DNA molecule comprises four basic building blocks, nucleotides. The genetic information carried within the molecule is determined by the order of the nucleotides. Knowledge of the order of these building blocks, which is known as the DNA sequence, is necessary for disease diagnostics and forensic DNA analysis, for example. Despite the great progress in recent years, the current DNA sequencing methods, typically based on fluorescent labelling, are still time-consuming and relatively expensive techniques, which have some limitations. Therefore, scientists are intensively searching for new approaches to simplify and accelerate sequencing.

One promising approach is the use of electrochemical detection and so-called redox labels, which are compounds that can be oxidized or reduced on electrodes. A multidisciplinary team of researchers from IOCB Prague, URV, the Faculty of Science of Charles University, the Polish Academy of Sciences, and the Institute of Biophysics of the Czech Academy of Sciences, with students David Kodr and Cansu Pinar Yenice as first authors, has now succeeded in designing and synthesizing artificial nucleotides with special attached redox labels that can be oxidized on a gold or carbon electrode at a specific potential to produce a measurable and analytically useful signal. These labels are carboranes, cage structures composed of boron and carbon atoms, into which other metal atoms can be incorporated, such as iron or cobalt, affecting their resulting electrochemical properties.

Publication: Michal Hocek, et al., Novel method of labeling DNA bases for sequencing, UOCHB IOCB Prague (2023). DOI: 10.1021/jacs.1c02222

Original Story Source: Czech Academy of Sciences