NMR-based fragment screening, Frankfurt, Germany

Service Availability:

Remote

Physical

Instruments Available:

BMRZ has significantly expanded its capacity in fragment- and drug-screening for both RNAs and proteins. Two dedicated spectrometers (600 MHz) are optimized for screening using 1.7 mm, 3.0 mm, and 5.0 mm probes, including specialized ¹⁹F and low-gamma detection probes.

User Guide

The BMRZ has significantly expanded its capacity for fragment- and drug-screening of both RNA and protein targets. Two dedicated 600 MHz NMR spectrometers are optimized for screening applications and equipped with 1.7 mm, 3.0 mm, and 5.0 mm probes, including specialized 19F and low-γ detection probes.

Researchers can perform screening campaigns using either:

Their own compound libraries, or
The in-house DSI-poised library, consisting of approximately 600 well-characterized fragments, developed for efficient hit discovery and follow-up studies.

These resources, together with the automated NMR infrastructure, enable high-throughput and reproducible fragment-screening workflows for a wide range of biomolecular targets.

Sample Preparation Guidelines

For each screening experiment, prepare two types of NMR samples:

Reference (blank) sample – ligand mixture without the target biomolecule.
Target sample – ligand mixture in the presence of the target (protein, RNA, or DNA).

NMR tube options and sample volumes:

1.7 mm tubes: 30 µL sample volume – highly advantageous when biomolecule availability is limited, minimizing sample consumption.
3.0 mm tubes: 200 µL sample volume – standard format for most screening experiments.
5.0 mm tubes: 500 µL sample volume – suitable for large-scale or concentration-insensitive assays.

For sample setup, use standard Bruker NMR tubes compatible with HT sample changers.

Transfer the biomolecular target (e.g., ¹H screening: 10 µM RNA or protein) in the defined screening buffer into the selected NMR tube (final volume as above) either manually or using a pipetting robot.

Each NMR tube’s barcode ID is automatically linked to the acquired dataset, ensuring a fully traceable, ID-based workflow. The robotic temperature-control system maintains constant conditions during sample preparation and measurement.

Further Information and Support

For detailed methodology and step-by-step setup, users are strongly encouraged to consult the Facility’s publication in the Journal of Visualized Experiments (JoVE):

“NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode” DOI: 10.3791/62262

Before planning or conducting any screening experiment, please discuss your project with the Facility’s scientific experts to ensure optimized, target-specific screening conditions: Christian Richter and Sridhar Sreeramulu (Early consultation with the team helps develop a user-tailored screening strategy, ensuring efficient use of available instrumentation, samples, and screening resources.)

Availability: yes

Physical access: yes

Remote access: yes

Average time of a visit 1-2d