Dr Iva Hopkins Navratilova
The characterization of biomolecular interactions is essential for modern drug discovery. Each drug, whether it is a protein, peptide or small chemical molecule has to go through a process of identification, efficiency improvement and toxicology tests before it is sent to the clinical trials. Surface plasmon resonance (SPR)-based biosensor technology offers a great flexibility in which type of target it can be applied to and covers a wide range of applications from small molecules, peptides, proteins, antibodies, nucleic acids, membranes to whole cells and viruses. SPR biosensor-based assays are well suited to overcoming many of the limitations of traditional binding assays. SPR detection methods eliminate the need to label reagents, thereby avoiding the risk that the label may interfere with complex formation or radioactive disposal. SPR analyzers are able to monitor complex formation in real time and therefore can be used to resolve a number of kinetic and thermodynamic parameters and mechanism of an interaction. Biosensors are particularly useful for translational biology as, unlike other biochemical screening or biophysical methods they can be utilized across the drug discovery and development pipeline for both small molecules and biological drugs. For example, biosensor screening can be used for fragment screening and, increasingly, for high-throughput screening; during the medicinal chemistry optimization process, SPR methods can provide detail characterization drug binding and various pharmacokinetic parameters. SPR can also aid understand of toxicity by enabling cross-screening against ‘antitargets’ simultaneously; in the clinical development stage, biosensor methods are particularly valuable for measuring biomarkers in the either laboratory or clinical setting.
Biophysical analysis of GPCRs
One of emerging applications of SPR is measuring interactions between small molecules and G-protein coupled receptors (GPCRs). The SPR methods being developing in our laboratory are capable of measuring the direct kinetic characterisation of GPCRs interactions with their natural ligands or low molecular weight inhibitors. Compared to alternative technologies (radioligand assays, whole cell assays) SPR provides direct measurement of the interactions without introducing any non-specific interactions of ligands to proteins on cells, the assay once developed is easy and time effective to perform. Kinetic information obtained is then important for further compound design optimisation for this important class of drug targets.