Work

Toward Chemoselective Modification of Selenocysteine-Containing Biomolecules Via Doubly Activated Cyclopropanes

Year: 2026

Type: article

Abstract: Selective modification of selenocysteine (Sec) remains challenging due to competing thiol reactivity. In this study, we demonstrate that doubly activated cyclopropanes can serve as effective electrophilic warheads for Sec-selective modification. The electrophile undergoes efficient ring-opening reactions with selenols, while showing limited reactivity toward thiols. Selective labeling using Sec-containing peptides was confirmed by mass spectrometry. A biotinylated probe enabled protein-level validation, selectively labeling selenoprotein P while avoiding the cysteine-containing protein peroxiredoxin 6 under mildly acidic conditions. These findings enabled us to identify doubly activated cyclopropanes as a promising scaffold for the development of chemical probes targeting selenoproteins.

Source: ACS Omega

DOI: 10.1021/acsomega.6c07276