TCO-PEG8-TCO
CAS No.: 2353409-67-1
Cat No.: BP-501150
Purity: 95%
4.5 
TCO-PEG8-TCO is a bifunctional, polyethylene glycol–based PROTAC linker bearing two trans-cyclooctene (TCO) groups at the termini. The PEG segment provides a hydrophilic, conformationally flexible spacer of defined length, while the TCO moieties serve as strained-alkene handles for rapid bioorthogonal conjugation via inverse-electron-demand Diels–Alder reactions with complementary tetrazines. In PROTAC design, this linker enables modular assembly by coupling two different targeting or effector components—such as an antibody fragment, ligand, or small-molecule binder—through sequential tetrazine–TCO ligations, allowing controlled placement and improved effective molarity at the target interface. The dual-reactive architecture supports efficient, orthogonal-like pairing under mild conditions, facilitating synthesis of homogeneous targeted protein degraders and enabling optimization of linker geometry to tune ternary complex formation and degradation potency.
Structure of 2353409-67-1
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* For research and manufacturing use only. Not for human or clinical use.
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TCO-PEG8-TCO is a bifunctional, PEG-based PROTAC linker designed to connect two trans-cyclooctene (TCO) handles for efficient, modular assembly of targeted protein degraders. Its flexible ether-rich chain supports productive spatial presentation of reactive termini, while the dual TCO functionality enables controlled conjugation strategies commonly used in PROTAC workflows. The detailed structural and reactivity considerations for constructing PROTACs with this linker are provided below.
Structure: The linker comprises a polyethylene glycol scaffold bearing two trans-cyclooctene moieties at the termini. It contains ether linkages characteristic of PEG flexibility and carbon–carbon/unsaturated features within the TCO rings. Overall, the structure is designed to balance solubility, conformational freedom, and reactive handle accessibility.
Reactivity: TCO groups undergo rapid, bioorthogonal inverse-electron-demand cycloaddition with tetrazines, typically proceeding under mild conditions compatible with biomolecule conjugation. PROTAC assembly using this linker generally involves preparing TCO-bearing intermediates and then reacting them with tetrazine-functional partners to form stable cycloadducts. Solvent systems that maintain solubility of both components and preserve protein-binding functionality are commonly employed; catalysts are generally not required for the cycloaddition step.
* 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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