ArticleBioconjugate chemistry2015
Enhancing reactivity for bioorthogonal pretargeting by unmasking antibody-conjugated trans-cyclooctenes.
Article in Bioconjugate chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- Tetrazine Ligation in Living Systems: Beyond Fast Kinetics to Effective Bioorthogonality.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Review
- Pharmacokinetic Optimization of Radiocopper-Based Theranostic Pretargeting.Molecular pharmaceutics · 2026Article
- Enhanced-mRNA Delivery Using Ultrasound-Delivered Anchors for Bioorthogonal Ligation.Angewandte Chemie (International ed. in English) · 2026Article
- Click Chemistry Enables [Bioconjugate chemistry · 2024Article
- Characterization of Structurally DiverseACS omega · 2023Article
- Quantitative Analysis and Optimization of Site-Specific Protein Bioconjugation in Mammalian Cells.Bioconjugate chemistry · 2022Article
- A bispecific, crosslinking lectibody activates cytotoxic T cells and induces cancer cell death.Journal of translational medicine · 2022Article
- Tmem65 is critical for the structure and function of the intercalated discs in mouse hearts.Nature communications · 2022Article
- Phasor Analysis of Fluorescence Lifetime Enables Quantitative Multiplexed Molecular Imaging of Three Probes.Analytical chemistry · 2022Article
- IEDDA: An Attractive Bioorthogonal Reaction for Biomedical Applications.Molecules (Basel, Switzerland) · 2021Review
- Expanding the Scope of Antibody Rebridging with New Pyridazinedione-TCO Constructs.Bioconjugate chemistry · 2020Article
- Preclinical Evaluation of a NovelACS omega · 2020Article
- Targeted and modular architectural polymers employing bioorthogonal chemistry for quantitative therapeutic delivery.Chemical science · 2020Article
- Pushing the limits of detection for proteins secreted from single cells using quantum dots.The Analyst · 2019Article
- A Single-Step Chemoenzymatic Reaction for the Construction of Antibody-Cell Conjugates.ACS central science · 2018Article
- An Efficient Method for Labeling Single Domain Antibody Fragments withBioconjugate chemistry · 2018Article
- Hydrophilic azaspiroalkenes as robust bioorthogonal reporters.Chemical communications (Cambridge, England) · 2018Article
- Pretargeting of internalizing trastuzumab and cetuximab with aEJNMMI research · 2017Article
- Antibody PEGylation in bioorthogonal pretargeting with trans-cyclooctene/tetrazine cycloaddition: in vitro and in vivo evaluation in colorectal cancer models.Scientific reports · 2017Article
- Spirohexene-Tetrazine Ligation Enables Bioorthogonal Labeling of Class B G Protein-Coupled Receptors in Live Cells.Journal of the American Chemical Society · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The bioorthogonal cycloaddition reaction between tetrazine and trans-cyclooctene (TCO) is rapidly growing in use for molecular imaging and cell-based diagnostics. We have surprisingly uncovered that the majority of TCOs conjugated to monoclonal antibodies using standard amine-coupling procedures are nonreactive. We show that antibody-bound TCOs are not inactivated by trans-cis isomerization and that the bulky cycloaddition reaction is not sterically hindered. Instead, TCOs are likely masked by hydrophobic interactions with the antibody. We show that introducing TCO via hydrophilic poly(ethylene glycol) (PEG) linkers can fully preserve reactivity, resulting in >5-fold enhancement in functional density without affecting antibody binding. This is accomplished using a novel dual bioorthogonal approach in which heterobifunctional dibenzylcyclooctyne (DBCO)-PEG-TCO molecules are reacted with azido-antibodies. Improved imaging capabilities are demonstrated for different cancer biomarkers using tetrazine-modified fluorophore and quantum dot probes. We believe that the PEG linkers prevent TCOs from burying within the antibody during conjugation, which could be relevant to other bioorthogonal tags and biomolecules. We expect the improved TCO reactivity obtained using the reported methods will significantly advance bioorthogonal pretargeting applications.
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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.