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Related Experiment Videos

An ultraefficient affinity-based high-throughout screening process: application to bacterial cell wall biosynthesis

Kenneth M Comess1, Mark E Schurdak, Martin J Voorbach

  • 1Department of Target and Lead Discovery, Global Pharmaceutical R&D, Abbott Laboratories, Abbott Park, Illinois 60064-6217, USA. kenneth.m.comess@abbott.com

Journal of Biomolecular Screening
|September 16, 2006
PubMed
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Researchers discovered novel inhibitors for Streptococcus pneumoniae

Area of Science:

  • Biochemistry
  • Medicinal Chemistry
  • Drug Discovery

Background:

  • Streptococcus pneumoniae poses a significant threat, necessitating new therapeutic strategies.
  • Targeting essential bacterial enzymes like MurF is crucial for developing effective antibiotics.
  • Novel screening methods are vital for identifying potent and selective drug candidates.

Purpose of the Study:

  • To discover a new class of inhibitors for the Streptococcus pneumoniae cell wall biosynthesis enzyme, MurF.
  • To develop and validate a novel affinity screening strategy for identifying selective enzyme inhibitors.
  • To demonstrate the applicability of this strategy for various protein targets and ligand libraries.

Main Methods:

  • Employed a novel affinity screening approach utilizing equilibrium binding.

Related Experiment Videos

  • Integrated iterative ultrafiltration steps for compound enrichment.
  • Utilized mass spectrometry for ligand identification.
  • Implemented electronic subtraction to remove non-selective compounds and identify MurF-specific ligands.

    • Main Results:

    • Successfully identified a new class of specific inhibitors for the MurF enzyme.
    • Demonstrated the effectiveness of the novel screening strategy in distinguishing selective ligands from promiscuous compounds.
    • Validated the method's ability to bypass traditional selectivity panels.

    Conclusions:

    • The developed affinity screening strategy is highly effective for discovering specific enzyme inhibitors.
    • This method offers a robust platform for identifying novel drug candidates against essential bacterial targets.
    • The approach is broadly applicable to diverse soluble protein targets and ligand libraries, advancing drug discovery efforts.