TCO-PEG12-TFP ester
Cat No.: BP-501827
4.5 
TCO-PEG12-TFP ester is a bifunctional, polyethylene glycol–based PROTAC linker that combines a trans-cyclooctene (TCO) reactive handle with a terminal tetrafluorophenyl (TFP) ester for amide-bond formation. Structurally, it features a long, flexible PEG chain that spaces the two reactive domains, improving solubility and reducing steric interference during conjugation. In PROTAC and targeted degradation workflows, the TFP ester enables efficient coupling to primary amines on ligands such as targeting moieties or protein-binding modules, forming stable amide linkages. The TCO group can subsequently participate in rapid, bioorthogonal inverse-electron-demand Diels–Alder chemistry with tetrazine-functional partners, allowing modular assembly of larger degraders or conjugates under mild conditions. This linker is valuable for constructing well-defined, distance-controlled degraders, facilitating optimization of effective ternary complex formation and improving experimental reproducibility in targeted protein degradation research.
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* For research and manufacturing use only. Not for human or clinical use.
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TCO-PEG12-TFP ester is a bifunctional PROTAC linker designed to combine a strained trans-cyclooctene (TCO) handle with a reactive tetrafluorophenyl (TFP) ester for efficient conjugation. Its PEG-based spacer provides hydrophilicity and spatial separation between functional groups for modular conjugation workflows. The detailed structural and reactivity considerations for PROTAC construction are provided below.
Structure: The linker comprises a TCO moiety connected through a long, flexible PEG chain to a TFP activated ester. It contains strained-ring alkene functionality, ether linkages within the PEG segment, and an acyl-activated carboxylate ester suitable for nucleophilic substitution.
Reactivity: The activated ester reacts with primary amines (e.g., lysine-containing ligands) to form stable amide bonds under mild aqueous or mixed-solvent conditions. The TCO group undergoes rapid inverse-electron-demand Diels–Alder (IEDDA) ligation with tetrazines for bioorthogonal conjugation; trans-to-cis isomerization reduces TCO reactivity and is not used as a coupling strategy. Use anhydrous, amine-free handling for the ester; select buffers that minimize competing hydrolysis, and avoid strong nucleophiles until the desired coupling step is complete.
* 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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