TCO-PEG3-TCO
CAS No.: 2243569-22-2
Cat No.: BP-500432
Purity: 95%
4.5 
TCO-PEG3-TCO is a bifunctional, polyethylene glycol–based linker bearing two trans-cyclooctene (TCO) moieties at both termini, separated by a short PEG3 spacer that provides aqueous solubility and conformational flexibility. In PROTAC and related targeted degradation designs, the TCO groups enable rapid, bioorthogonal ligation via inverse-electron-demand Diels–Alder chemistry with complementary tetrazine-functional partners, allowing modular conjugation of two different components under mild conditions. This design facilitates efficient assembly of degrader constructs by bringing together a ligand for the target protein and a ligand for an E3 ubiquitin ligase through a stable covalent linkage formed after reaction, while the PEG spacer helps reduce steric hindrance and can improve effective intramolecular reach. The product is therefore valuable for researchers optimizing linker length, reaction compatibility, and degradation performance in TCO–tetrazine PROTAC workflows.
Structure of 2243569-22-2
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* For research and manufacturing use only. Not for human or clinical use.
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TCO-PEG3-TCO is a bifunctional, polyethylene glycol–containing linker designed for efficient PROTAC assembly via trans-cyclooctene (TCO) chemistry. Its extended, flexible PEG segment can improve productive ternary complex formation by modulating linker length and conformational mobility. The dual TCO handles enable sequential conjugation to complementary partners, supporting robust, modular synthesis workflows. Detailed structural and reactivity considerations are provided below.
Structure: The linker comprises two trans-cyclooctene moieties connected through a short PEG spacer, providing a flexible, ether-rich backbone. It features strained alkene rings characteristic of TCO groups and multiple ether linkages that enhance solubility and conformational adaptability in polar organic media.
Reactivity: TCO-functional linkers typically react through strain-promoted inverse-electron-demand cycloaddition with tetrazines, enabling rapid, bioorthogonal conjugation under mild conditions. For PROTAC construction, the linker is commonly used to install or exchange one binding handle at a time, using appropriate tetrazine-bearing partners. Reactions are generally performed in compatible solvents that maintain solubility while preserving TCO stability; catalysts are usually unnecessary, though temperature and pH should be optimized to prevent premature hydrolysis or degradation of reactive intermediates.
* 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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