Fragment Screening and Fragment Based Drug Design

SARomics Biostructures technology platform offers a unique and proprietary weak affinity chromatography (WAC™) technology for fragment screening. WAC™ provides a robust, accurate and high throughput (2000-3000 cmpds/week) way for fragment library screening.

The technology
The WAC™
method is based on covalent immobilisation 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. Ligand efficiency and ligand binding energy may subsequently be calculated.

A general discussion of drug discovery strategies is presented on our technology section.

Below are the three WAC™ options offered

WAC™ pilot
Description

• Limited screen of small library < 50 fragments
• Client supply protein
• Preparation of column with immobilized protein
• Screening in duplicates
• Useful as feasibility step for large WAC™ screen
• Fixed price and fast turnaround

Deliverables
• List of hits sorted after Δt
ret
• Short report with technical details

Download pdf…

Proprietary fragment library
Our library includes a collection of 1300 fragments (available as neat sample, DMSO and DMSO-d6 solutions).
• Designed to be general purpose, (not target-directed) covering diverse chemical space.
• A focus on low-molecular weight fragments (<220)
• Solubility data (DMSO, water) are available for >80% of the fragments
• Analytical data (LCMS, 1H-NMR) available for all fragments
• Designed to be MedChem friendly (HBDs, HBAs and ring count, ClogP, functional groups, etc)
• >90% commercially available facilitating rapid SAR-generation

Exclusive small libraries is also an option available through our academic MedChem collaborations.