Methyltetrazine-PEG4-SSPy
Cat No.: BP-501816
4.5 
Methyltetrazine-PEG4-SSPy is a heterobifunctional PROTAC linker featuring a methyltetrazine bioorthogonal handle, a four-unit polyethylene glycol (PEG) spacer, and a disulfide (SS) linkage that can be reduced in intracellular environments. The methyltetrazine motif is designed to participate in rapid inverse-electron-demand Diels–Alder chemistry with strained trans-cyclooctene or related dienophiles, enabling efficient conjugation of two molecular partners under mild conditions. The PEG4 segment provides conformational flexibility and improved aqueous solubility, which can reduce steric interference during assembly and help preserve productive geometry for ternary-complex formation. The disulfide linkage is positioned to allow intracellular cleavage, facilitating release or reconfiguration of the degraded-protein–recruiting construct after cellular entry. This linker is valuable for targeted protein degradation research because it supports modular synthesis of degraders, allows controlled intracellular processing, and can improve the practical manufacturability of conjugates for mechanistic and optimization studies.
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* For research and manufacturing use only. Not for human or clinical use.
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This PROTAC linker, Methyltetrazine-PEG4-SSPy, is designed to connect a tetrazine-based targeting handle to a thiol-reactive module through a polyethylene glycol spacer and a disulfide linkage. Its features support efficient assembly of bifunctional degraders and can facilitate controlled conjugation strategies that are commonly used to optimize intramolecular positioning and workflow compatibility in targeted protein degradation. The detailed structural and reactivity considerations are provided below.
Structure: The linker incorporates a tetrazine moiety for bioorthogonal conjugation, a PEG4 ethylene glycol spacer to enhance solubility and conformational flexibility, and a disulfide (SS) bond for redox-responsive connectivity. It contains heteroatoms that can participate in noncovalent interactions, improving compatibility with aqueous PROTAC workflows.
Reactivity: Tetrazine functionality is suitable for inverse-electron-demand Diels–Alder ligation with strained alkenes or related dienophiles under mild, aqueous-compatible conditions, enabling modular PROTAC assembly. The disulfide linkage supports thiol/disulfide exchange or reduction-dependent cleavage pathways, which can be leveraged to tune intracellular release behavior. Conjugation is typically performed with appropriate buffering, controlled stoichiometry, and purification to remove unreacted components; catalysts are generally not required for the tetrazine ligation 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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