Methyltetrazine-PEG4-NHS Ester

Tetrazine-PEG4-NHS ester is an amine-reactive labeling reagent with enhanced water solubility provided by a PEG4 spacer.


  • Biocompatible – click reaction occurs efficiently under mild buffer conditions; requires no accessory reagents such as a copper catalyst or reducing agents (e.g. DTT)
  • Chemoselective – tetzines and trans-cyclooctene groups do not react or interfere with other functional groups found in biological samples but conjugate to one another with high efficiency
  • Unprecedented kinetics – inverse-electron demand Diels-Alder chemistry is the fastest bioorthogonal ligation available, delivering conjugates within 30 min at 1 mg/mL concentrations
  • Primary amine reactivity – modify amine-containing molecules with tetrazine moiety for use in advanced crosslinking experiments
  • Highly stable – tetrazine functional group remains stable in aqueous buffered media (weeks at 4C, pH 7.5)
  • Extended PEG4 Spacer – reduces aggregation, minimizes steric hindrance, and enhances solubility

Tetrazine-PEG4-NHS ester reacts specifically and efficiently with a primary amine (e.g., side chain of lysine residues or aminosilane-coated surfaces) at pH 7-9 to form a covalent bond. The hydrophilic polyethylene glycol (PEG) spacer arm imparts water solubility that is transferred to the labeled molecule, thus reducing aggregation of labeled proteins stored in solution. The PEG spacer arm provides a long and flexible connection that minimizes steric hindrance involved with ligation to complementary TCO-containing molecules.

Catalog Number Product DataSheet Size AVAILABILITY Price Qty
Methyltetrazine-PEG4-NHS Ester, 4 x 2 mg
4 x 2mg In stock
Regular Price:$186.00
On Sale:
Methyltetrazine-PEG4-NHS Ester, 10 mg
10mg In stock
Regular Price:$171.00
On Sale:
Methyltetrazine-PEG4-NHS Ester, 25 mg
25mg In stock
Regular Price:$326.00
On Sale:
Methyltetrazine-PEG4-NHS Ester, 100 mg
100mg In stock
Regular Price:$729.00
On Sale:

Product Type: Small Molecule
Name: Tetrazine-PEG5-NHS Ester
Chemical Formula: C24H31N5O9
Molecular Weight: 533.53
Variant MPN: 1069
Purity: >95%, HPLC
Solubility: DMSO, DMF, MeOH, DCM, THF
Storage: -20C. Desiccate
Shipped: Ambient


Applications: Protein-protein conjugation, protein-antibody conjugation, protein-small molecule conjugation, 18F radiolabeling, protein-oligonucleotide conjugation, surface modification

  1. Sudath Hapuarachchige, Yoshinori Kato & Dmitri Artemov. Bioorthogonal two-component drug delivery in HER2(+) breast cancer mouse models. Scientific Reports 6, Article number: 24298 (2016). doi:10.1038/srep24298
  2. Blackman, M. L., et. al. (2008). "Tetrazine Ligation: Fast Bioconjugation Based on Inverse- Electron-Demand Diels-Alder Reactivity." J. Am. Chem. Soc., 130:13518-13519
  3. Devaraj, N. K., et. al. (2008) "Tetrazine-Based Cycloadditions: Application to Pretargeted Live Cell Imaging." Bioconjugate Chem., 19(12): 2297–2299.
  4. Devaraj, N. K., et. al. (2009) "Fast and Sensitive Pre-Targeted Labeling of Cancer Cells through a Tetrazine/trans-Cyclooctene Cycloaddition." Angew. Chem. Int. Ed.
  5. Haun, J.B., et. al. (2009) " Probing Intracellular Biomarkers and Mediators of Cell Activation Using Nanosensor and Bioorthogonal Chemistry" ACS Nano., 5:3204-321
  6. Ryan JM, Mittal P, Menoret A, Svedova J, Wasser JS, Adler AJ, Vella AT. A novel biologic platform elicits profound T cell costimulatory activity and antitumor immunity in mice. Cancer Immunol Immunother. 2018 Apr;67(4):605-613. 

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