CD BioSciences offers our clients advanced biophysical techniques to assess the stability of proteins, providing them with information to gain insight into compound-target interactions. Our cost-effective and high-throughput screening methods will help accelerate our clients' drug discovery progress and reduce drug development costs.

Background

Differential scanning fluorescence (DSF), often referred to as thermal shift analysis (TSA), is a convenient and rapid method for high throughput drug screening and target discovery. It allows rapid assessment of protein stability based on the temperature at which protein melts in presence of fluorescent dye, Sypro orange. TSA has been widely used in the study of protein stability (protein thermal stability parameters and their influencing factors), protein structure and conformation, protein-ligand interactions and protein stabilizers, inhibitors and cofactors due to its advantages of low protein sample loss, high throughput, a wide range of temperature variation and accurate data.

TSA techniques offer the potential to account for factors that contribute to the folding and stability of native biomolecules, including hydrophobic interactions, hydrogen bonding, conformational entropy and the physical environment. The accurate and high-quality data obtained from TSA can provide important information about the stability of proteins during process development and the formulation of potential therapeutic drug candidates.

Fig.1 An example melting curve demonstrating protein denaturation with increasing temperature. (Samuel, 2021)

Our Services

With our advanced biophysical analysis platform, we provide our clients with the following measurement services:

• Identification of ligands that bind to the target, buffer conditions, and cofactors.
• Analysis of protein thermal stability.
• Optimization of buffer formulations and cofactors to promote protein stability.
• Provide major reader domain proteins, including chromodomains, bromodomains, and other methyl-readers.
• Selection of fragments representing different binding categories from primary screening.

Applications

• Identify and select the most stable proteins or potential drug candidates for biotherapeutic drug development.
• Research on ligand interactions.
• Study on inhibition mechanism of small molecular compounds.
• Rapid determination of optimal conditions for liquid formulations.
• Stability indication analysis of target proteins for screening.

Advantages of Our Technology Platform

• Low sample consumption.
• Allows viewing of overlapping melting curves across different measurement conditions.
• Large-scale screening capability to characterize thousands of compounds in a short time.
• High throughput screening methods and accurate data acquisition.

Our Workflow

The research team at CD BioSciences has expertise as well as extensive experience in studying the target involvement of drug candidates with the application of TSA. We provide scientific assistance for our clients in quantifying the extent to which drug candidates bind to protein targets and in assessing protein stability. If you are interested in our services, please contact us to enquire about our TSA services.

Reference

1. Samuel, E. L. G.; et al. Processing binding data using an open-source workflow. Journal of Cheminformatics. 2021, 13(1): 1-11.

• Drug Design Based on X-ray Crystallography
• Thermodynamic Characterization of Biomolecular Interactions
• Target Binding Analysis by HDX-MS
• Binding Affinity Measurement by MST
• Fragment Screening Based on WAC
• Hit Identification by NMR-based Techniques
• Qualification of Targeting Protein-Protein Interactions
• Measurement of Ligand Binding Kinetics
• Identification of Small-Molecule Aggregation
• Analysis of Free Energy Calculations
• Modeling of Scaffold Hopping Transformations
• Cellular Imaging Service for Drug Discovery
• AFM-Based Biophysical Analysis of Drugs