Methyltetrazine-PEG8-N3
Cat No.: BP-502013
4.5 
Methyltetrazine-PEG8-N3 is a heterobifunctional polyethylene glycol linker combining a methyltetrazine moiety with an azide (N3) terminus through an extended PEG chain. Structurally, it provides a flexible, hydrophilic spacer that separates the two reactive handles, improving accessibility and reducing steric interference in conjugation workflows. In PROTAC and related targeted degradation designs, the methyltetrazine group serves as a strained-alkene/biorthogonal partner for rapid inverse-electron-demand Diels–Alder ligation, enabling site-specific attachment to a compatible trans-cyclooctene or similar handle-bearing ligand, while the terminal azide supports orthogonal “click” chemistry (e.g., with cyclooctyne or related alkyne partners) for subsequent functionalization. This dual-reactivity and long, PEG-mediated reach make the linker valuable for assembling modular degraders, optimizing linker length for productive ternary complex formation, and facilitating iterative synthesis of PROTACs with controlled conjugation sites for mechanistic and structure–activity studies.
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* For research and manufacturing use only. Not for human or clinical use.
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Methyltetrazine-PEG8-N3 is a bifunctional PROTAC linker designed to connect a tetrazine-bearing targeting module with an azide-functional partner through orthogonal chemistries. Its key advantage is compatibility with widely used bioorthogonal conjugation strategies, enabling efficient assembly of degraders under conditions that are generally compatible with sensitive biomolecular ligands. The linker’s PEG-based segment also supports favorable solubility and conformational flexibility, which can improve productive ternary complex formation. Detailed structural and reactivity considerations are provided below.
Structure: The linker incorporates a methyltetrazine moiety and an azide (N3) handle connected through a polyethylene glycol chain. It contains heteroaromatic nitrogen-rich functionality and ether linkages characteristic of PEG, providing a flexible, hydrophilic scaffold with a defined reactive tetrazine site.
Reactivity: The methyltetrazine group is suited for inverse-electron-demand Diels–Alder reactions with strained dienes (commonly trans-cyclooctene or bicyclononyne derivatives) to form stable conjugates. The terminal azide enables copper-free or copper-assisted azide–alkyne cycloaddition to attach complementary alkyne-bearing ligands. Typical assembly uses inert atmospheres when needed, polar aprotic or aqueous-compatible solvents, and catalysts such as Cu(I) only when compatible with the biomolecule and desired chemoselectivity.
* 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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