The objective of this project is to develop a human telomeric DNA electrochemical biosensor for the rapid screening of drugs able to induce and stabilise quadruplex DNA structures, overcoming the inhibition and/or disruption effects caused by shelterin POT1 proteins that protect the ends of chromosomes.
Telomeres are responsible for the protection of the ends of linear chromosomes and are involved in more than 80% of all cancers. The electrochemical biosensor consists of human telomeric d[AG3(T2AG3)3] sequences self-assembled in the presence of shelterin POT1 proteins that specifically recognise single-stranded telomeric DNA and prevent quadruplex formation. The biosensor enables the rapid screening of anticancer drugs targeting telomeric and/or oncogene sequences, such as BRACO-19 and TMPyP4, overcoming the inhibition and/or disruption effects caused by POT1 and preventing the telomeric DNA ends from opening to telomerase, thus indirectly inhibiting the activity of the telomerase enzyme complex.