TCO-PEG24-NHS ester
TCO-PEG24-NHS ester is a polyethylene glycol (PEG)–based PROTAC linker bearing a trans-cyclooctene (TCO) moiety and an N-hydroxysuccinimide (NHS) ester for efficient conjugation to primary amines. Structurally, the molecule combines a long, flexible PEG chain that provides aqueous solubility and spatial separation with a strained TCO handle that can undergo bioorthogonal inverse-electron-demand Diels–Alder reactions with tetrazine-functional partners. In PROTAC design, the NHS ester enables rapid attachment to lysine-containing ligands or affinity tags, while the TCO group serves as a reactive “click” site to connect the resulting conjugate to a tetrazine-bearing counterpart, thereby promoting controlled assembly of multi-component degraders. This linker is valuable for constructing modular targeted degradation systems, improving conjugation efficiency and tuning effective distance and orientation between binding and recruitment elements, which can be critical for maintaining ternary-complex formation and degradation potency.
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* For research and manufacturing use only. Not for human or clinical use.
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TCO-PEG24-NHS ester is a polyethylene glycol (PEG)-based bifunctional PROTAC linker designed to connect targeting ligands through an NHS-activated ester handle and to enable rapid bioorthogonal conjugation via a trans-cyclooctene (TCO) moiety. Its flexible PEG spacer supports favorable linker length and reduced steric constraints, while the TCO group provides a widely used click-like strategy for controlled assembly of ternary complexes in targeted protein degradation workflows. The following points describe the structure and practical reactivity considerations in detail below.
Structure: The molecule combines an NHS-activated ester for acyl transfer with a TCO functional group and a long, flexible PEG chain. It contains ester and ether linkages along the polymer backbone, plus an activated carbonyl susceptible to nucleophilic substitution, supporting aqueous compatibility and conformational flexibility.
Reactivity: The NHS ester reacts with primary amines under mild, water-compatible conditions to form stable amide bonds, typically requiring controlled pH and avoidance of competing nucleophiles such as excess amines or thiols. The TCO functionality participates in fast inverse-electron-demand cycloaddition with tetrazines, enabling stepwise PROTAC assembly. Common solvents include aqueous buffers with organic co-solvents when needed; catalysts are generally not required for either coupling 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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