TCO-Tetrazine Conjugation: Unmatched Speed, Precision, and Biocompatibility

TCO-Tetrazine conjugation is an advanced bioorthogonal reaction known for its exceptional speed, biocompatibility, and selectivity.

This chemistry is based on an inverse-demand Diels–Alder cycloaddition between trans-cyclooctene (TCO) and tetrazine, forming a stable dihydropyridazine bond. With ultrafast kinetics exceeding 800 M−1s−1, available enabling efficient conjugation at nanomolar to micromolar concentrations. This high reaction rate significantly reduces reagent usage and minimizes cytotoxicity risks.
Tco Tz Ligation Reaction
Schematic representation of a TCO-Tz ligation reaction.
in complex biological environments ensuring precise reactions. Unlike copper-based click chemistry reactions, TCO-Tetrazine conjugation does not require metal catalysts, thereby preserving cell viability and biological integrity. This makes it especially well-suited for live-cell imaging, in vivo studies, and other sensitive biological applications.
Beyond its broad use in in vivo applications, the unique properties of TCO-Tetrazine conjugation have also advanced research in cell and gene therapy, antibody-drug conjugates (ADCs), theranostics, and targeted drug delivery. Its precision, speed, and low cytotoxicity make TCO-Tetrazine conjugation a valuable tool across broad applications.
Vector Laboratories offers a comprehensive range of high-purity TCO and Tetrazine reagents delivering complete solutions for your experimental needs. With high purity, consistency, and rigorous quality control, our reagents ensure reproducibility, reliability, and high performance in the most sensitive and demanding applications.

Key Features of TCO-Tetrazine Reactions:

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Ultrafast Reaction Kinetics:
The fastest bioorthogonal reaction with rate constants exceeding 800 M−1s−1 enabling rapid and efficient labeling.
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High Specificity and Selectivity:
TCO-Tetrazine chemistry ensures minimal off-target effects offering exceptional precision in complex biological systems.
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Mild, Physiological Conditions:
Operates efficiently at physiological temperatures and pH preserving the natural environment of living cells and tissues.
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Low Concentration Functionality:
The high reactivity of TCO-Tetrazine enables effective conjugation at nanomolar to micromolar concentrations.
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Copper-Free Reaction:
No need for copper catalysts preserving cell viability and functionality in live-cell and in vivo applications.
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Broad Compatibility:
Suitable for conjugation of a wide range of biomolecules, including proteins, peptides, nucleic acids, lipids, and small molecules.

Key Benefits of TCO-Tetrazine Reactions:

Fast and Efficient Labeling at Low Concentrations:
The ultrafast kinetics of TCO-Tetrazine reactions allow for efficient conjugation even at low concentrations.
Low Cytotoxicity:
TCO-tetrazine conjugation avoids the cytotoxicity typically associated with copper-catalyzed reactions increasing the biocompatibility in live cells and tissues.
Preservation of Biomolecule Functionality:
High specificity of conjugation preserves activity of surrounding molecules in complex biological environments.

Broad Applicability of TCO-Tetrazine Reactions:

  • Live-Cell Labeling & In Vivo Imaging
  • Antibody-Drug Conjugates (ADCs) and other Targeted Drug Delivery
  • Click-to Release Chemistry
  • Super Resolution Microscopy
  • Biomolecule Conjugation (ex. proteins, peptides, glycans, nucleic acids, lipids, nanoparticles)
  • Targeted Drug Delivery
  • Metabolic Labeling
  • Surface Functionalization
  • Tissue Engineering
  • Theranostics
  • Fluorescence Imaging and Detection
Get in touch with us at
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to take the next step in your bioconjugate journey.