Synthesis of electrochemical probes for nucleic acid detection

We have developed new electrochemical probes for nucleic acid detection. A ferrocenyl phosphoramidite synthon has been synthesized and incorporated in stem–loop structured oligodeoxyribonucleotides (ODN), by automated solid-phase DNA synthesis. When spotting these “ferrocenyl molecular beacons” on a gold electrode microarray, a self-structuration of the probes occurred on the electrode surface. The hairpin structure opening, generated by the hybridization with the complementary nucleic acid target, induces both current intensity and potential variations of the ferrocenyl electrochemical signal by cyclic voltammetry. The effect of the ferrocene number in the sequence on hairpin thermodynamic stability and the electrochemical response of probes towards DNA target hybridization are studied. These ferrocene modified stem–loop ODNs allowed the detection of their complementary targets by cyclic voltammetry.