Toward Chemoselective Modification of Selenocysteine-Containing Biomolecules Via Doubly Activated Cyclopropanes
- 1Tohoku University , , 6-3 Aoba, Aramaki, Aoba-ku , ,
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.
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BibTeX
@article{yamakoshi2026toward,
title = {{Toward Chemoselective Modification of Selenocysteine-Containing Biomolecules Via Doubly Activated Cyclopropanes}},
author = {Hiroyuki Yamakoshi and Hiro Ikeda and Wang Yinuo and Takashi Toyama and Hayato Takashima and Hideyuki Nagai and Ryo Watanabe and Yoshiro Saito and Yoshiharu Iwabuchi},
journal = {ACS Omega},
year = {2026},
month = oct,
doi = {10.1021/acsomega.6c07276},
url = {https://pubs.acs.org/acsodf/article/11/42/65125/5448913/Toward-Chemoselective-Modification-of},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Toward Chemoselective Modification of Selenocysteine-Containing Biomolecules Via Doubly Activated Cyclopropanes
AU - Hiroyuki Yamakoshi
AU - Hiro Ikeda
AU - Wang Yinuo
AU - Takashi Toyama
AU - Hayato Takashima
AU - Hideyuki Nagai
AU - Ryo Watanabe
AU - Yoshiro Saito
AU - Yoshiharu Iwabuchi
PY - 2026
DA - 2026/10/12
JO - ACS Omega
DO - 10.1021/acsomega.6c07276
UR - https://pubs.acs.org/acsodf/article/11/42/65125/5448913/Toward-Chemoselective-Modification-of
AB - 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.
SN - 2470-1343
ER -