Spectroscopic Visualization of Drug–Biomolecules Interactions: An Insight to Fluorescence Quenching as Tool in Drug Discovery

Abstract

Fluorescence quenching, a process where the intensity of fluorescence is diminished by various molecular interactions, has emerged as a critical tool in drug discovery. This review delves into the underlying mechanisms of fluorescence quenching, including static and dynamic quenching, Förster resonance energy transfer (FRET), and photoinduced electron transfer (PET). Each mechanism offers unique insights into molecular interactions, binding affinities, and conformational changes of drug candidates, enabling researchers to dissect complex biological systems with precision. The application of fluorescence quenching in high-throughput screening (HTS) is particularly emphasized, highlighting its role in identifying lead compounds and optimizing drug–target interactions. Furthermore, the review explores the integration of advanced fluorescence techniques, such as time-resolved fluorescence and single-molecule spectroscopy, in elucidating the quenching phenomena at a molecular level. These techniques provide a deeper understanding of drug–receptor interactions, allosteric modulation, and protein dynamics, which are pivotal in the drug development pipeline. The potential of fluorescence quenching in probing the pharmacokinetics and pharmacodynamics of novel therapeutics is also discussed, underscoring its versatility and effectiveness. By offering a comprehensive analysis of fluorescence quenching mechanisms and their applications, this review aims to inform future drug discovery endeavors, fostering the development of more effective and targeted therapies.