Academic Journal
Organelle-Resolved Tetrazine-trans-Cyclooctene Click Chemistry for Cargo Delivery and Release.
| Τίτλος: | Organelle-Resolved Tetrazine-trans-Cyclooctene Click Chemistry for Cargo Delivery and Release. |
|---|---|
| Συγγραφείς: | Durydivka O; Department of Bioorganic and Medicinal Chemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic., Chovanec M; Department of Bioorganic and Medicinal Chemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic., Dzijak R; Department of Bioorganic and Medicinal Chemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic., Rahm M; Department of Bioorganic and Medicinal Chemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic., Hrusak J; Department of Bioorganic and Medicinal Chemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic., Reyes-Gutierrez PE; Department of Bioorganic and Medicinal Chemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic., Vrabel M; Department of Bioorganic and Medicinal Chemistry, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic. |
| Πηγή: | Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2026 Sep 19; Vol. 32 (35), pp. e71198. Date of Electronic Publication: 2026 Jun 01. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley-VCH Country of Publication: Germany NLM ID: 9513783 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-3765 (Electronic) Linking ISSN: 09476539 NLM ISO Abbreviation: Chemistry Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Weinheim, Germany : Wiley-VCH |
| Ιατρικοί όροι (MeSH): | Cyclooctanes*/chemistry , Doxorubicin*/chemistry , Prodrugs*/chemistry , Organelles*/chemistry , Organelles*/metabolism, Mitochondria/metabolism ; Mitochondria/chemistry ; Fluorescent Dyes/chemistry ; Click Chemistry ; Humans ; Cycloaddition Reaction ; Drug Delivery Systems ; Aza Compounds ; Benzene Derivatives |
| Περίληψη: | Accurate delivery of small molecules to specific cell compartments or organelles offers great potential for bioimaging and targeted therapy but remains challenging to predict and control. In this study, we evaluate a modular strategy for organelle-directed delivery based on organelle-targeting groups combined with tetrazine-trans-cyclooctene bioorthogonal chemistry. We demonstrate that organelle-targeting probes bearing tetrazine or trans-cyclooctene can efficiently undergo inverse-electron-demand Diels-Alder reactions within various cellular compartments, including the plasma membrane, mitochondria, nucleus, endoplasmic reticulum, and lysosomes. Using this method, we localize fluorophores and the cytotoxic drug doxorubicin to specific organelles in living cells. We further show that tetrazine- or trans-cyclooctene-modified doxorubicin prodrugs restore cytotoxic activity upon click-to-release activation inside cells. However, direct comparisons of different probe architectures revealed that organelle targeting and reaction efficiency are highly sensitive to structural context, cargo type, and subcellular environment, and cannot be predicted solely from targeting motifs. Overall, these findings establish a framework for comparing organelle-targeted bioorthogonal chemistry and offer practical guidance for designing probes and prodrugs that enable precise spatiotemporal control of small-molecule activity in living cells. (© 2026 The Author(s). Chemistry ‐ A European Journal published by Wiley‐VCH GmbH.) |
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(PMID: 30275469) |
| Grant Information: | 61388963 Academy of Sciences of the Czech Republic; LX22NPO5104 National Institute for Research of Metabolic and Cardiovascular Diseases; European Union; CZ.02.01.01/00/22_008/0004607 New Technologies for Translational Research in Pharmaceutical Sciences /NETPHARM |
| Contributed Indexing: | Keywords: click chemistry; doxorubicin; drug delivery; inverse‐electron‐demand Diels‐Alder reaction; live‐cell imaging; organelle targeting |
| Substance Nomenclature: | 0 (Cyclooctanes) 80168379AG (Doxorubicin) 0 (Prodrugs) 0 (Fluorescent Dyes) 0 (1,2,4,5-tetrazine) 0 (Aza Compounds) 0 (Benzene Derivatives) |
| Entry Date(s): | Date Created: 20260601 Date Completed: 20260918 Latest Revision: 20260920 |
| Update Code: | 20260920 |
| PubMed Central ID: | PMC13587637 |
| DOI: | 10.1002/chem.71198 |
| PMID: | 42225547 |
| Βάση Δεδομένων: | MEDLINE |
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