Aarhus University Seal / Aarhus Universitets segl

Thomas Poulsen

STEFs: Activated Vinylogous Protein-Reactive Electrophiles

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

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.

Original languageEnglish
JournalAngewandte Chemie - International Edition
Volume58
Issue11
Pages (from-to)3533-3537
Number of pages5
ISSN1433-7851
DOIs
Publication statusPublished - 2019

    Research areas

  • bioconjugation, cysteine, probes, proteomics, sulfur

See relations at Aarhus University Citationformats

ID: 150088607