ArticleACS chemical biology2013
A biocompatible in vivo ligation reaction and its application for noninvasive bioluminescent imaging of protease activity in living mice.
Article in ACS chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 60 citations in OpenAlex.
- Bioorthogonal Chemistry in Biomolecule Quantification: A Review of Reactions and Strategies.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Reactive Cysteines in Proteins are the Dominant Reductants for Platinum(IV) Prodrug Activation in Live Cells.Angewandte Chemie (International ed. in English) · 2025Article
- Light-Controlled Intracellular Synthesis of Poly(luciferin) Polymers Induces Cell Paraptosis.Journal of the American Chemical Society · 2025Article
- Quantitative analysis of electroporation-mediated intracellular delivery via bioorthogonal luminescent reaction.Communications chemistry · 2024Article
- The Application of Bio-orthogonality for In Vivo Animal Imaging.Chemical & biomedical imaging · 2023Review
- Portable bioluminescent platform for in vivo monitoring of biological processes in non-transgenic animals.Nature communications · 2021Article
- Recent progress in the imaging detection of enzyme activitiesRSC advances · 2019Review
- Cell-specific image-guided transcriptomics identifies complex injuries caused by ischemic acute kidney injury in mice.Communications biology · 2019Article
- Early-Stage Incorporation Strategy for Regioselective Labeling of Peptides using the 2-Cyanobenzothiazole/1,2-Aminothiol Bioorthogonal Click Reaction.ChemistryOpen · 2018Article
- In vivo bioluminescence imaging of labile iron accumulation in a murine model ofProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Rapid Access to a Broad Range of 6'-Substituted Firefly Luciferin Analogues Reveals Surprising Emitters and Inhibitors.Organic letters · 2017Article
- In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole.Beilstein journal of organic chemistry · 2016Article
- Small Molecule Active Site Directed Tools for Studying Human Caspases.Chemical reviews · 2015Review
- Article
- A biocompatible "split luciferin" reaction and its application for non-invasive bioluminescent imaging of protease activity in living animals.Current protocols in chemical biology · 2014Article
- Beyond D-luciferin: expanding the scope of bioluminescence imaging in vivo.Current opinion in chemical biology · 2014Review
- Bioluminescence: a versatile technique for imaging cellular and molecular features.MedChemComm · 2014Article
- trans-Cyclooctene--a stable, voracious dienophile for bioorthogonal labeling.Current opinion in chemical biology · 2013Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The discovery of biocompatible reactions had a tremendous impact on chemical biology, allowing the study of numerous biological processes directly in complex systems. However, despite the fact that multiple biocompatible reactions have been developed in the past decade, very few work well in living mice. Here we report that D-cysteine and 2-cyanobenzothiazoles can selectively react with each other in vivo to generate a luciferin substrate for firefly luciferase. The success of this "split luciferin" ligation reaction has important implications for both in vivo imaging and biocompatible labeling strategies. First, the production of a luciferin substrate can be visualized in a live mouse by bioluminescence imaging (BLI) and furthermore allows interrogation of targeted tissues using a "caged" luciferin approach. We therefore applied this reaction to the real-time noninvasive imaging of apoptosis associated with caspase 3/7. Caspase-dependent release of free D-cysteine from the caspase 3/7 peptide substrate Asp-Glu-Val-Asp-D-Cys (DEVD-(D-Cys)) allowed selective reaction with 6-amino-2-cyanobenzothiazole (NH(2)-CBT) in vivo to form 6-amino-D-luciferin with subsequent light emission from luciferase. Importantly, this strategy was found to be superior to the commercially available DEVD-aminoluciferin substrate for imaging of caspase 3/7 activity. Moreover, the split luciferin approach enables the modular construction of bioluminogenic sensors, where either or both reaction partners could be caged to report on multiple biological events. Lastly, the luciferin ligation reaction is 3 orders of magnitude faster than Staudinger ligation, suggesting further applications for both bioluminescence and specific molecular targeting in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.