DNA-ELECTROCHEMICAL BIOSSENSOR APLICATIONS IN THE
INVESTIGATION OF DRUG-DNA INTERACTION MECHANISMS
W. B. S. Machini and A. M. Oliveira-Brett
Department of Chemistry, Faculty of Science and Technology,
University of Coimbra, 3004-535, Coimbra, Portugal
wbmachini@ipn.pt
A DNA-electrochemical biosensor consists of a device in which the DNA is immobilized
on the electrochemical transducer surface to detect specific binding processes with
different molecules, to monitor changes in the DNA conformational structure after
interaction with these molecules, and the appearance of DNA base residues and their
oxidation products, the biomarkers of DNA oxidative damage.
The DNA-electrochemical biosensors in the investigation of drug-DNA interaction have
enabled to elucidate the drugs implications in DNA structural modifications, and the
mechanistic and cytotoxic aspects of their physiological action.
The interaction between different drugs, such as the antileishmanial miltefosine, the
antidiabetic metformin, and the anticancer monoclonal antibody nivolumab, with dsDNA,
in incubated solutions using differential pulse voltammetry, UV-Visible
spectrophotometry, and/or gel electrophoresis, was investigated. The drugs-DNA
interaction was also evaluated using the dsDNA-, poly[G]- and poly[A]-electrochemical
biosensors, by differential pulse voltammetry, electrochemical impedance spectroscopy
and/or quartz crystal microbalance.
The changes in the dsDNA structural morphological conformation observed were related
to the condensation and/or aggregation, distortion and/or unwinding of the double helix,
binding of the molecules in the DNA grooves, and release of guanine and adenine residues.
The drugs-dsDNA interaction mechanisms were proposed.
Acknowledgements: PhD Grant 232296/2014-6 (W.B.S. Machini) from CNPq/Brazil,
projects FCT (UID/EMS/00285/2013) and Innovec'EAU (SOE1/P1/F0173).
[1] W. B. S. Machini, A. M. Oliveira-Brett. Electroanalysis, 2018, 30, 48-56.
[2] W. B. S. Machini, I. P. G. Fernandes, A. M. Oliveira-Brett, Electroanalysis, 2019, In
press.