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NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode
09:19

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

Published on: June 4, 2021

Screening a fragment cocktail library using ultrafiltration.

Sayaka Shibata1, Zhongsheng Zhang, Konstantin V Korotkov

  • 1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.

Analytical and Bioanalytical Chemistry
|July 14, 2011
PubMed
Summary
This summary is machine-generated.

Ultrafiltration screening identifies potential drug ligands for protein targets. This fragment-based drug discovery method is efficient for targets with typical binding affinities.

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Last Updated: May 31, 2026

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Fragment-based drug discovery (FBDD) is crucial for identifying novel therapeutic leads.
  • Identifying ligands with millimolar to micromolar dissociation constants (K(d)) is a common challenge in FBDD.
  • High-throughput screening methods are needed to accelerate ligand discovery for protein targets.

Purpose of the Study:

  • To adapt ultrafiltration for a 96-well format suitable for FBDD.
  • To screen fragment-sized molecules against medical structural genomics target proteins.
  • To validate the ultrafiltration method for identifying protein-ligand interactions.

Main Methods:

  • Ultrafiltration coupled with a 96-well format was employed.
  • Cocktails of small molecules (150-300 Da) were screened.
  • Competitive binding assays were used to confirm ligand interactions.

Main Results:

  • The ultrafiltration method successfully identified potential ligands for protein targets.
  • Screening was effective for identifying molecules within the typical FBDD affinity range.
  • Method validation confirmed the reliability of identified interactions.

Conclusions:

  • Ultrafiltration is a versatile and effective method for fragment-based drug discovery.
  • The 96-well format enhances throughput for screening small molecule libraries.
  • This approach aids in identifying novel ligands for protein targets in structural genomics.