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Related Concept Videos

Affinity Chromatography01:03

Affinity Chromatography

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Affinity chromatography is a powerful technique extensively utilized for separating and purifying specific biomolecules from complex mixtures. It capitalizes on the highly selective binding between an analyte and its counterpart, such as antibody-antigen interactions. The counterpart is immobilized on the stationary phase, forming an affinity column. The stationary phase typically consists of solid support, such as agarose or porous glass beads, immobilizing the affinity ligand. The mobile...
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High-Throughput Binder Confirmation Using Affinity Selection Mass Spectrometry.

Eric X Shi1

  • 1Encoded Library Technologies/NCE Molecular Discovery, R&D Medicinal Science and Technology, GlaxoSmithKline, Cambridge, MA, USA. xiangguo.e.shi@gsk.com.

Methods in Molecular Biology (Clifton, N.J.)
|September 9, 2022
PubMed
Summary
This summary is machine-generated.

Affinity selection mass spectrometry (AS-MS) on a new high-throughput binder confirmation (HTBC) platform efficiently assesses target engagement. This method aids in prioritizing synthesis for DNA-encoded library technology hits.

Keywords:
Affinity selectionDNA-encoded library (DEL)ELTLigandMass spectrometryProteinsScreeningSmall molecules

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Area of Science:

  • Biochemistry
  • Analytical Chemistry
  • Drug Discovery

Background:

  • DNA-encoded library technology (ELT) enables rapid screening of vast chemical libraries.
  • Prioritizing ELT hits for synthesis requires efficient target engagement assessment.
  • Traditional methods can be time-consuming and resource-intensive.

Purpose of the Study:

  • To introduce and evaluate a novel high-throughput binder confirmation (HTBC) platform.
  • To assess the utility of Affinity Selection Mass Spectrometry (AS-MS) within the HTBC platform.
  • To demonstrate the platform's capability in prioritizing chemical series for synthesis.

Main Methods:

  • Integration of Affinity Selection Mass Spectrometry (AS-MS) into a High-Throughput Binder Confirmation (HTBC) workflow.
  • Application of the HTBC-AS-MS platform to evaluate target engagement across numerous chemical series.
  • Utilizing the platform at GSK for decision-making in organic synthesis prioritization.

Main Results:

  • The HTBC-AS-MS platform successfully assesses target engagement for hundreds of chemical series per target.
  • Demonstrated efficiency in evaluating a large number of potential drug candidates.
  • Enabled rapid prioritization of synthesis decisions for ELT hits.

Conclusions:

  • The HTBC-AS-MS platform is a powerful tool for accelerating drug discovery.
  • This integrated approach significantly enhances the efficiency of hit-to-lead optimization.
  • The platform facilitates informed synthesis decisions, optimizing resource allocation in medicinal chemistry.