Tetrazine-Ph-PEG5-Ph-tetrazine
Cat No.: BP-502064
4.5 
Tetrazine-Ph-PEG5-Ph-tetrazine is a homobifunctional PEG-based linker engineered for bioorthogonal conjugation via the inverse electron-demand Diels–Alder reaction between tetrazine and strained dienes (commonly trans-cyclooctene or norbornene derivatives). Structurally, it comprises two tetrazine moieties connected through phenyl spacers and a five-unit polyethylene glycol segment, providing both chemical reactivity and aqueous solubility. In PROTAC and targeted protein degradation workflows, such a linker can be used to modularly assemble degraders by enabling rapid, catalyst-free coupling of tetrazine-bearing and diene-bearing components, thereby positioning warhead and E3-ligase ligands with controlled flexibility. The PEG chain helps reduce steric hindrance and can improve effective reach and conjugate stability in biological media. This makes Tetrazine-Ph-PEG5-Ph-tetrazine valuable for constructing multi-component degradation constructs, optimizing linker length, and facilitating iterative synthesis of structure–activity relationships in targeted degradation research.
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* For research and manufacturing use only. Not for human or clinical use.
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Tetrazine-Ph-PEG5-Ph-tetrazine is a bifunctional, PEG-based linker designed to support efficient assembly of PROTAC constructs through tetrazine-mediated bioorthogonal conjugation. Its flexible poly(ethylene glycol) spacer and aromatic termini help tune solubility and spatial presentation of reactive groups, which can improve effective ternary complex formation. The molecule is described in detail below, including its structure and practical reactivity considerations for PROTAC linker chemistry.
Structure: The linker contains two tetrazine units connected through a conjugated aromatic framework and a flexible PEG chain. It features heteroaromatic tetrazine rings, ether linkages within the PEG segment, and carbon–carbon and carbon–heteroatom bonds that provide conformational flexibility and stable covalent attachment points.
Reactivity: Tetrazine groups are typically used in inverse-electron-demand Diels–Alder reactions with strained dienes such as trans-cyclooctene derivatives under mild, aqueous-compatible conditions. For PROTAC assembly, the linker is commonly reacted with complementary tetrazine-reactive partners to form stable conjugates via a cycloaddition mechanism. Solvent systems that maintain tetrazine stability and diene reactivity are selected, and reaction progress is monitored by analytical methods appropriate for heteroaromatic conjugation chemistry.
* 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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