TCO-PEG4-TCO
TCO-PEG4-TCO is a bifunctional polyethylene glycol linker bearing two trans-cyclooctene (TCO) groups separated by a short PEG4 spacer. Structurally, it provides a flexible, water-compatible conjugation handle while presenting TCO moieties that undergo rapid, bioorthogonal inverse-electron-demand Diels–Alder reactions with tetrazine-functional partners. In PROTAC and targeted degradation workflows, this linker can be used to connect or exchange two molecular components—such as a ligand-recruiter module and an E3 ligase binder—by enabling efficient, catalyst-free TCO–tetrazine ligation under conditions compatible with sensitive biomolecules. The PEG spacer helps maintain productive geometry and reduces steric hindrance, which can improve the probability of forming a stable ternary complex between the recruited protein and the target-binding moiety. As a result, TCO-PEG4-TCO is valuable for constructing modular PROTACs, performing late-stage conjugation, and optimizing linker length and flexibility in targeted protein degradation studies.
Structure of 2243569-23-3
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* For research and manufacturing use only. Not for human or clinical use.
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TCO-PEG4-TCO is a bifunctional, polyethylene glycol–based linker designed for PROTAC assembly and related targeted degradation workflows that rely on bioorthogonal tetrazine–trans-cyclooctene chemistry. Its dual TCO handles enable modular conjugation to two binding partners, supporting efficient construction of degraders with controlled connectivity and improved solubility. The points below describe its structure and practical reactivity considerations in PROTAC-relevant reaction design.
Structure: The linker contains two trans-cyclooctene (TCO) moieties connected through a PEG spacer, providing flexible, ether-rich connectivity. It features carbon–carbon unsaturation within the TCO units and multiple ether linkages in the PEG chain, contributing to favorable hydrophilicity and conformational mobility for conjugation.
Reactivity: TCO groups undergo rapid, catalyst-free inverse-electron-demand Diels–Alder reactions with tetrazines under aqueous, near-neutral conditions typical of PROTAC conjugation workflows. Reactivity is driven by the strained alkene in TCO and the electrophilicity of tetrazines, forming a cycloadduct suitable for stable linkage. Use tetrazine partners in compatible buffers; minimize exposure to light and avoid conditions that promote TCO isomerization or degradation.
* 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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