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·2025
Easy Access to Bioorthogonal Click-to-Release Reagent Bishydroxy-<i>trans</i>-cyclooctene (C<sub>2</sub>TCO) and Harnessing of Its Rapid Labeling and Dissecting Feature in Multicycle Imaging
V. Arun, Minju Lee, Hongseo Choi, Sang‐Woo Lee, Junwon Choi, Tae Hyeon Yoo, Wook Kim, Eunha Kim
IF 3.9Bioconjugate Chemistry
초록

Bifunctional <i>trans</i>-cyclooctene (bTCO) with a carbamate or carbonate at the allylic position and tetrazine provide a promising bioorthogonal click chemistry pair for the click-to-release approach, successfully employed in various biotechnological applications. Herein, we demonstrate a simple and straightforward method to synthesize C<sub>2</sub>TCO, a symmetrical bTCO derivative with two hydroxyl groups at the allylic positions. The efficiently synthesized C<sub>2</sub>TCO at first was selectively functionalized with a fluorophore (C<sub>2</sub>TCO-FL), and the conjugate was labeled onto monoclonal antibodies (Ab-C<sub>2</sub>TCO-FL). The fluorophore of Ab-C<sub>2</sub>TCO-FL was easily removed from the antibody through the mild treatment of tetrazine, enabling multicycle fluorescent bioimaging. Next, an antibody-drug conjugate targeting PD-L1 was prepared using the linker based on C<sub>2</sub>TCO. The cytotoxic payload was efficiently released from the antibody upon tetrazine treatment, which induced cellular cytotoxicity.

키워드
Bioorthogonal chemistryChemistryCycloocteneReagentClick chemistryFeature (linguistics)Combinatorial chemistryNanotechnologyOrganic chemistryCatalysis
타입
article
IF / 인용수
3.9 / 1
게재 연도
2025