CD BioSciences is committed to providing scientific services and technical support to our clients at multiple stages of drug discovery. Our team helps clients effectively study weak interactions and provide fragment screening services through weak affinity chromatography (WAC) technology, thereby improving the chances of successful drug development.

Background

Fragment-based drug discovery/design (FBDD) is based on the concept of discovering small fragments (<300-350 in molecular weight) that show weak but efficient binding to target molecules (e.g. protein receptors). Since fragments inherently have a weak affinity for their targets, the development of assays with high sensitivity to affinity is important to achieve fragment screening.

A major challenge in screening weakly binding fragments is the difficulty in detecting binding interactions at equilibrium and the need to screen at high concentrations. A number of biophysical methods are available, such as MS, NMR, X-ray crystallography and SPR. Weak affinity chromatography (WAC) has recently been introduced as a new technique for fragment screening. The technique is based on the weak partitioning affinity separation of analytes (e.g. small molecules) and represents a simple and robust fragment screening technique. WAC is now a potential method for drug discovery for fragment screening due to the characteristics of sensitivity, cost-effectiveness and easily accessible.

Fig.1 Schematic demonstration of WAC-MS. (Ohlson, 2018)

Our Services

Our researchers have worked to establish the WAC method and develop it into a new method for fragment screening and affinity determination in early drug discovery. Furthermore, we continually optimize our fragment screening procedures to achieve high throughput operation on standard instruments with minimal consumption of target proteins and samples. The services we offer include, but are not limited to:

• Purification of analytes from any crude form of sample.
• Affinity determination and ranking.
• Screening of stereoisomers.
• Identification and characterization of contaminants, degradation products, and chiral compounds.
• Kinetic determination.
• Optimize throughput, minimize the number of targets, and expand the affinity ranges to be seen for fragments.

Applications

• Evaluation of potential binders of interest in natural mixtures and organic synthetic mixtures.
• Research on diverse targets with larger libraries of fragments.
• Application in early stages of hit development.

Advantages of Us

• Provide WAC as a valuable complement to other technologies for fragment screening, such as functionalization determination, NMR, X-ray crystallography and SPR.
• Highly accurate, flexible and easy-to-use screening strategies.
• Time-saved and cost-effective services.

Based on extensive experience in drug discovery and advanced biophysical technologies, CD BioSciences offers clients a combination of technologies to enable fragment screening. Furthermore, we continually optimize our data acquisition software to save data processing time and thus increase throughput. If you are interested in our services, please contact us to enquire about our WAC services.

Reference

1. Ohlson, S.; Duong-Thi, M. D. Fragment screening for drug leads by weak affinity chromatography (WAC-MS). Methods. 2018, 146: 26-38.

• Drug Design Based on X-ray Crystallography
• Thermodynamic Characterization of Biomolecular Interactions
• Target Binding Analysis by HDX-MS
• Binding Affinity Measurement by MST
• Protein Stability Evaluation by TSA
• 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