NMR-based Fragment Screening in a Minimum Sample but Maximum Automation Mode

Area of Science:

• Biochemistry and Structural Biology
• Medicinal Chemistry
• Drug Discovery

Background:

• Fragment-based screening (FBS) is a crucial technique in drug discovery for identifying low-affinity binders.
• NMR-based fragment screening provides high sensitivity, purity assessment, and quality control of fragment libraries.
• Current academic FBS is often manual, limiting infrastructure and accessibility for drug and chemical probe development.

Purpose of the Study:

• To present advanced, automated workflows for NMR-based fragment screening.
• To improve the economic feasibility and throughput of fragment screening processes.
• To broaden the accessibility of established protocols for biomacromolecular research.

Main Methods:

• Utilized state-of-the-art hardware for automated, temperature-controlled sample preparation and NMR tube filling.
• Implemented automated 1H/19F NMR ligand-based spectral acquisition at controlled temperatures.
• Employed high-throughput sample changers capable of handling over 500 samples and advanced software for accelerated data analysis.

Main Results:

• Demonstrated automated workflows that significantly speed up data acquisition and analysis in NMR-based FBS.
• Enabled efficient quality control of fragment libraries, including solubility and chemical integrity.
• Established protocols for screening protein and RNA samples, enhancing usability for researchers.

Conclusions:

• Advanced automated workflows enhance the efficiency, throughput, and accessibility of NMR-based fragment screening.
• These optimized protocols support both academic and industrial drug discovery and chemical probe development.
• The presented methods facilitate broader application of FBS in biomacromolecular research.