Fragment based approaches in drug discovery (FBDD) have gained high popularity in drug discovery and development processes as alternatives to traditional high throughput screening methods. SARomics Biostructures technology platform offers several biophysical methods for fragment screening, hit identification and structure-based drug discovery (SBDD). In addition, our unique and proprietary weak affinity chromatography (WAC™) technology provides a robust, accurate and high throughput (2000-3000 cmpds/week) way for fragment library screening.
Weak affinity chromatography technology
The WAC™ method is based on covalent immobilization of a protein to be screened on a standard high-performance liquid chromatograph (HPLC) column. The solution of small molecular weight fragments is subsequently injected into the column. During elution, the fragments that have higher affinity for the protein will stay on the column longer than those with low or no affinity. The fragments can be conveniently detected using mass or UV spectrometry. This method is an efficient and lower-cost choice, compared to other methods that study ligand binding, e.g., X-ray crystallography, NMR spectroscopy or isothermal titration calorimetry (ITC). After the initial hit identification, NMR spectroscopy and X-ray crystallography may be used to gain additional insights into the details of the interactions of the fragments with the protein binding site, the amino acid resides involved in the interactions, types of interactions, etc. These in turn can be used, e.g., in calculation of ligand efficiency or ligand binding energy.
A general discussion of drug discovery strategies is presented on our technology section.
Below are the three WAC™ options offered.