Methyltetrazine-PEG5-methyltetrazine
Cat No.: BP-502104
4.5 
Methyltetrazine-PEG5-methyltetrazine is a bifunctional polyethylene glycol linker bearing two methyl-substituted tetrazine termini connected through a five-unit PEG chain. The tetrazine groups serve as highly reactive handles for inverse-electron-demand Diels–Alder ligation with strained dienes such as trans-cyclooctene or bicyclononyne, enabling rapid, bioorthogonal conjugation under mild conditions. In PROTAC and targeted protein degradation workflows, this linker can be used to assemble modular constructs by installing one tetrazine-bearing end on a ligand that recruits an E3 ubiquitin ligase and the other end on a ligand that engages the target protein, with the PEG segment providing solubility and conformational flexibility to support productive ternary complex formation. Its value lies in facilitating efficient, orthogonal, and tunable linker chemistry, allowing researchers to rapidly generate and optimize degradation agents while minimizing off-target reactivity from nonselective coupling chemistries.
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* For research and manufacturing use only. Not for human or clinical use.
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Methyltetrazine-PEG5-methyltetrazine is a bifunctional, PEG-based linker designed to support PROTAC assembly through tetrazine-mediated bioorthogonal chemistry. Its dual methyltetrazine termini enable efficient conjugation to complementary strained-alkene partners, allowing modular construction of targeted protein degraders. The flexible PEG spacer can help tune linker length and conformational dynamics, which may improve productive ternary complex formation. Detailed structural and synthetic considerations are provided below.
Structure: The linker contains two methyltetrazine moieties connected by a polyethylene glycol chain, providing a flexible, hydrophilic spacer. It features aromatic heterocycles (tetrazine) and ether linkages within the PEG backbone, with overall properties consistent with improved solubility and reduced aggregation in aqueous PROTAC workflows.
Reactivity: Tetrazine groups undergo inverse-electron-demand Diels–Alder reactions with strained alkenes (commonly trans-cyclooctene or related dienophiles) under mild, aqueous-compatible conditions. For PROTAC synthesis, the linker is typically reacted with a strained-alkene–functionalized ligand in a suitable buffer or solvent system, often with careful control of pH and temperature to preserve tetrazine integrity. No metal catalysts are generally required, and the reaction proceeds via a rapid click-type mechanism to form a stable conjugate.
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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