Albany 2001

category image Biomolecular
SUNY at Albany
June 19-23, 2001

Electron Transfer Through DNA-Modified Surfaces: Detection of Single Base Mismatches and Other Perturbations to the Base Stack

DNA-based sensors have potential applications that range from genomic sequencing and mutation analysis to pathogen identification. The exquisite sensitivity of DNA electron transfer to minor perturbations in DNA structure and base stacking makes it an ideal platform for DNA sensing. A new electrocatalytic method for the detection of single base mismatches as well as DNA base lesions in fully hybridized duplexes has been developed based on charge transport through DNA films. Gold electrodes modified with pre-assembled DNA duplexes are used to monitor the electrocatalytic signal of methylene blue, a redox active DNA intercalator, coupled to ferricyanide. The presence of mismatched or damaged DNA bases substantially diminishes the electrocatalytic signal. All single base mismatches, including thermodynamically stable GT and GA mismatches, can be detected using this technology without stringent conditions for hybridization since this assay is not a measure of differential hybridization. Mismatches are also detected in DNA/RNA hybrid duplexes and assays for detection in genomic samples are being developed. DNA charge-transport sensing technology is now being applied also to investigate the nature of DNA-protein interactions and the mechanism of DNA-binding drugs.

Elizabeth M. Boon (1), Michael G. Hill (2), and Jacqueline K. Barton (1)

(1) California Institute of Technology, Division of Chemistry and Chemical Engineering, Pasadena, CA 91125 Phone: (626) 395-3200; Fax: (626) 577-4976; email: jkbarton@caltech.edu (2) Occidental College, Department of Chemistry, Los Angeles, CA 90041