Related Experiment Video
Updated: Jan 31, 2026

Monitoring On-Target Signaling Responses in Larval Zebrafish - Z-REX Unmasks Precise Mechanisms of Electrophilic Drugs and Metabolites
Published on: June 2, 2023
STEFs: Activated Vinylogous Protein-Reactive Electrophiles
Bente K Hansen1, Christopher J Loveridge1, Stine Thyssen2
1Department of Chemistry, Aarhus University, Langelandsgade 140, 8000, Aarhus C, Denmark.
Abstract:
Reported here is the synthesis of a class of semi-oxamide vinylogous thioesters, designated STEFs, and the use of these agents as new electrophilic warheads. This work includes preparation of simple probes that contain this reactive motif as well as its installation on a more complex kinase inhibitor scaffold. A key aspect of STEFs is their reactivity towards both thiol and amine groups. Shown here is that amine conjugations in peptidic and proteinogenic samples can be facilitated by initial, fast conjugation to proximal thiol residues. Evidence that both the selectivity and the reactivity can be tuned by the structure of STEFs is provided, and given the unique ability of this functionality to conjugate by an addition-elimination mechanism, STEFs are electrophilic warheads that could find broad use in chemical biology.
Related Concept Videos
Radical Reactivity: Electrophilic Radicals
Electrophiles
While a positive electrophile, like a proton, reacts due to its vacant, low-energy 1s orbital, the...
Activation and Inactivation of G Proteins
Regioselectivity of Electrophilic Additions-Peroxide Effect
Cross-reactivity
Reactivity of Enols

