Investigation of Proteome-Tetrazine Reactivity for a Highly Selective Tetrazine Ligation in Live Cells

Authors
Park, JunyoungHahm, JuheeYim, JunhyeongLee, HyelimHwang, Hwan MinLee, SoyeonPark, Ju-YoungVelladurai, ArunGangasani, Jagadeesh KumarCho, HanaPark, HankumLee, MinjuLee, JeeheeEom, HyunukSong, Woon JuLee, SangheeKim, EunhaPark, Jongmin
Issue Date
2025-06
Publisher
ACS Publications
Citation
ACS Central Science, v.11, no.6, pp.878 - 889
Abstract
Tetrazine has been widely used in bio-orthogonal click chemistry for diverse biological applications due to its short reaction time and excellent bio-orthogonality. For efficient click reaction, the stability of tetrazine in physiological conditions is one of the key issues in biological applications. However, the reactions between tetrazine and biomolecules have barely been studied. Here, we investigated nonspecific proteome labeling by tetrazine derivatives. Systematic investigation of proteome reactivities of 23 tetrazine derivatives showed their structure-dependent proteome reactivities. We further investigated the relationship between the proteome reactivity of tetrazine derivatives and selectivity of in situ tetrazine-trans-cyclooctene (Tz-TCO) click chemistry-mediated fluorescent labeling of BTK protein in live cells. Intriguingly, a tetrazine derivative SiR-Tz20 with minimal proteome reactivity showed a highly selective BTK labeling efficiency in live cells and in an ex vivo mouse model. Our results demonstrate that the proteome reactivity of tetrazine derivatives is critical for their selectivity in click reaction toward accurate fluorescent protein imaging in live cells.
Keywords
CHEMISTRY; BTK
ISSN
2374-7943
URI
https://pubs.kist.re.kr/handle/201004/152456
DOI
10.1021/acscentsci.5c00525
Appears in Collections:
KIST Article > Others
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