FRET-Based Probe for High-Throughput DNA Intercalator Drug Discovery and In Vivo Imaging

• DOI: 10.1021/acssensors.1c00167
• Publication Date: 2021-05-24T21:48:50Z
• Authors: Chandrashekhar U....; Samata Chaudhuri; Ibtissem Nabti; Hala Fahs; Fatima S. M. Refai; Xin Xie; Yanthe E. Pearson; Kristin C. Gunsalus; George T. Shubeita
• Keywords: High-Throughput Screening

Molecules that bind DNA by intercalating its bases remain among the most potent cancer therapies and antimicrobials due to their interference with DNA-processing proteins. To accelerate discovery of novel drugs, we designed a fluorescence resonance energy transfer (FRET)-based probe reports on intercalation, allowing rapid sensitive screening chemical libraries in high-throughput format. We demonstrate method correctly identifies known intercalators approved drug discover previously unreported compounds. When introduced cells, oligonucleotide-based rapidly distributes nucleus, direct imaging dynamics entry interaction native environment. This enabled us directly correlate potency killing cultured cells ability penetrate cell membrane. The combined capability single identify vitro follow function vivo can play valuable role accelerating DNA-intercalating drugs or repurposing ones.