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Related Concept Videos

Nuclear Binding Energy02:13

Nuclear Binding Energy

The difference between the calculated and experimentally measured masses is known as the mass defect of the atom. In the case of helium-4, the mass defect indicates a “loss” in mass of 4.0331 amu – 4.0026 amu = 0.0305 amu. The loss in mass accompanying the formation of an atom from protons, neutrons, and electrons is due to the conversion of that mass into energy that is evolved as the atom forms. The nuclear binding energy is the energy produced when the atoms’ nucleons are bound together;...
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Many heavier elements with smaller binding energies per nucleon can decompose into more stable elements that have intermediate mass numbers and larger binding energies per nucleon—that is, mass numbers and binding energies per nucleon that are closer to the “peak” of the binding energy graph near 56. Sometimes neutrons are also produced. This decomposition of a large nucleus into smaller pieces is called fission. The breaking is rather random with the formation of a large number of different...
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Covalent Fragment Screening Using the Quantitative Irreversible Tethering Assay
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A FRET-Based Assay for Assessing Covalent Warhead Reactivity.

Anna P Valaka1, Carlos Benitez-Martin1, Joakim Andréasson2

  • 1Department of Chemistry and Molecular Biology, University of Gothenburg, 405 30 Gothenburg, Sweden.

ACS Omega
|July 10, 2026
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Summary

This study introduces a novel fluorescent sensor to measure the reactivity of covalent drug warheads with biological molecules. The platform enables high-throughput screening, advancing drug discovery and chemical biology research.

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Area of Science:

  • Chemical Biology
  • Drug Discovery
  • Biochemistry

Background:

  • Covalent modalities are crucial in drug discovery but evaluating electrophilic warhead reactivity is challenging.
  • Förster resonance energy transfer (FRET)-based sensors are common in chemical biology but not used for warhead reactivity.
  • Assessing covalent warhead reactivity requires reliable and high-throughput methods.

Purpose of the Study:

  • To develop and validate a FRET-based fluorescent platform for assessing covalent warhead reactivity.
  • To quantify the reactivity of a sulfone-based nucleophilic aromatic substitution (SNAr) warhead toward biological nucleophiles.
  • To establish a high-throughput assay for screening nucleophiles and reaction conditions.

Main Methods:

  • Designed a FRET dyad incorporating a coumarin donor, dinitrophenyl quencher, and SNAr warhead.
  • Utilized the SNAr reaction to disrupt FRET, enabling fluorescence readout.
  • Performed assays in a 96-well plate format for high-throughput screening.

Main Results:

  • The FRET-based sensor effectively quantifies covalent warhead reactivity.
  • Demonstrated strong selectivity for thiols as nucleophiles.
  • The 96-well plate format facilitates high-throughput screening of nucleophiles and conditions.

Conclusions:

  • Developed a versatile and robust FRET-based fluorescent platform for evaluating covalent warhead reactivity.
  • This approach facilitates mechanistic studies in chemical biology and accelerates drug discovery.
  • The sensor shows promise for assessing drug-target interactions involving covalent modifications.