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Updated: Sep 3, 2025

A Semi-High-Throughput Adaptation of the NADH-Coupled ATPase Assay for Screening Small Molecule Inhibitors
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Biomacromolecule-Assisted Screening for Reaction Discovery and Catalyst Optimization.

Stephany M Ramos De Dios1, Virendra K Tiwari2, Christopher D McCune2

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Biomacromolecules like enzymes, antibodies, and nucleic acids enable sensitive and selective reaction discovery in experimental organic chemistry. These biological sensors facilitate the identification of novel chemical transformations and catalysts.

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Area of Science:

  • Synthetic Organic Chemistry
  • Biocatalysis
  • Chemical Biology

Background:

  • Catalyst screening and reaction discovery are fundamental to synthetic organic chemistry.
  • While computational methods advance, experimental approaches remain crucial.
  • Biomacromolecules offer unique sensing capabilities for chemical transformations.

Purpose of the Study:

  • To review biomacromolecule-assisted screening methods for reaction discovery.
  • To discuss the application of enzymes, antibodies, and nucleic acids as chemical sensors.
  • To highlight the subsequent elaboration of chemistry discovered through these methods.

Main Methods:

  • Utilizing native biomacromolecule chirality for product chirality readout.
  • Employing enzymatic sensing for UV-spectrophotometric and colorimetric detection.
  • Implementing antibody-based sensors with fluorescent or Enzyme-Linked ImmunoSorbent Assay (ELISA) readouts.
  • Leveraging DNA-encoded libraries for templation and reactant barcoding in screening.

Main Results:

  • Biomacromolecule-based screens demonstrate high sensitivity and selectivity.
  • Enzymatic screening identified Ni(0)-mediated asymmetric allylic amination and thiocyanopalladation/carbocyclization.
  • Enzyme-Linked ImmunoSorbent Assay (ELISA) screening discovered novel sydnone-alkyne cycloadditions.
  • DNA-encoded screening uncovered oxidative palladium-mediated amido-alkyne/alkene coupling reactions.

Conclusions:

  • Biomacromolecule-assisted screening is a powerful strategy for discovering novel chemical reactions and catalysts.
  • These methods exploit the inherent chirality and sensing capabilities of biological molecules.
  • The discovered reactions expand the toolkit for synthetic organic chemists.