TCO-PEG11-TCO
Cat No.: BP-501996
4.5 
TCO-PEG11-TCO is a bifunctional, polyethylene glycol–based linker bearing two trans-cyclooctene (TCO) groups at the termini, providing a flexible, water-compatible spacer of extended length between the reactive handles. In PROTAC and related targeted degradation designs, the TCO moieties serve as strained-alkene “click” partners that can undergo rapid, catalyst-free inverse-electron-demand Diels–Alder reactions with complementary tetrazine-functionalized ligands or recruiting modules. This enables efficient, modular conjugation of two molecular components while minimizing nonspecific crosslinking, and the PEG segment helps preserve solubility and reduces steric hindrance during ternary complex formation. The dual-TCO architecture is particularly valuable for constructing multi-component degraders, including systems that require sequential or orthogonal attachment of targeting and E3-recruiting elements, thereby improving experimental throughput and enabling systematic linker-length optimization for evaluating degradation potency and selectivity.
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* For research and manufacturing use only. Not for human or clinical use.
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TCO-PEG11-TCO is a bifunctional, PEG-based PROTAC linker designed to connect two tetrazine-reactive TCO termini, enabling efficient assembly of targeted protein degradation constructs. Its flexible polyethylene glycol scaffold supports productive spatial organization between ligands, while the complementary TCO handles facilitate rapid, bioorthogonal conjugation to tetrazine-bearing partners. The resulting modular architecture is well suited for researchers optimizing linker length, conformational freedom, and conjugation efficiency; detailed structural and reactivity considerations are provided below.
Structure: The linker comprises a long, flexible PEG chain terminated with two cyclooctene-based TCO moieties. It contains ether linkages typical of polyethylene glycol, providing conformational flexibility and improved solubility. The TCO units are alkene-containing functional groups positioned for subsequent tetrazine-triggered coupling.
Reactivity: TCO groups undergo strain-promoted inverse-electron-demand cycloaddition with tetrazines under mild, aqueous-compatible conditions, forming stable conjugates without requiring metal catalysts. For PROTAC construction, tetrazine-functionalized ligands are typically reacted with the TCO-terminated linker in suitable buffers, with reaction progress monitored by analytical methods such as LC-MS or HPLC. The PEG scaffold generally supports efficient conjugation by reducing steric constraints and maintaining solubility.
* 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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