HyNic-PEG2-TCO
Cat No.: BP-501927
4.5 
HyNic-PEG2-TCO is a bifunctional, PEG-based PROTAC linker bearing a hydrazine-containing “HyNic” handle and a strained trans-cyclooctene (TCO) moiety. Structurally, it provides a short, flexible ethylene glycol spacer that separates the conjugation sites, helping to reduce steric interference during subsequent assembly and improving the accessibility of each reactive group. In targeted protein degradation workflows, the HyNic functionality can be used to form hydrazone linkages with aldehyde-bearing partners, enabling modular coupling to one PROTAC component, while the TCO group serves as a clickable handle for rapid tetrazine-mediated ligation with a complementary Tz-functionalized partner. This combination supports efficient, chemoselective construction of multi-component degraders and facilitates the generation of linkers that maintain productive proximity between the ligand-binding elements and the recruited E3 ligase. The short PEG spacer and orthogonal reactivity make this reagent valuable for optimizing conjugation efficiency and degradation performance in experimental PROTAC design.
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* For research and manufacturing use only. Not for human or clinical use.
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HyNic-PEG2-TCO is a bifunctional PROTAC linker designed to connect a hydrazine-derived handle with a strained trans-cyclooctene (TCO) moiety through a short polyethylene glycol (PEG) spacer. This architecture supports efficient formation of targeted protein degraders by enabling rapid, bioorthogonal conjugation chemistry and by improving linker flexibility and effective reach between binding and recruiting elements. The detailed structural and reactivity characteristics are provided below.
Structure: The linker contains a PEG-based ethylene glycol segment that imparts conformational flexibility and hydrophilicity, coupled to a TCO alkene embedded in a strained cyclooctene framework. A hydrazine (HyNic) functional group provides a reactive nucleophilic site for downstream conjugation, with stable covalent linkages connecting these domains.
Reactivity: TCO groups typically undergo fast, strain-promoted inverse electron-demand cycloaddition with tetrazines under mild, aqueous-compatible conditions, enabling rapid conjugation without added catalysts. The HyNic handle is commonly used in hydrazone/related coupling workflows, where reaction efficiency depends on pH, buffer composition, and the electrophile partner. For PROTAC assembly, select solvents and concentrations that preserve TCO reactivity and maintain protein-ligand stability.
* 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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