Methyltetrazine-PEG4-maleimide
CAS No.: 1802908-02-6
Cat No.: BP-500749
Purity: 98%
4.5 
Methyltetrazine-PEG4-maleimide is a bifunctional PEG-based linker designed for modular PROTAC and targeted protein degradation workflows. Structurally, it combines a methyltetrazine moiety for bioorthogonal inverse-electron-demand Diels–Alder reactivity with a terminal maleimide group that selectively reacts with thiols, enabling sequential or orthogonal conjugation strategies. The PEG4 spacer provides a flexible, hydrophilic chain that can reduce steric interference, improve accessibility of reactive handles, and help preserve binding properties of the attached ligands. In PROTAC design, this linker can be used to install a tetrazine-bearing component onto a degradation platform and subsequently couple it to a thiol-functionalized partner (e.g., a ligand, targeting moiety, or carrier), or to perform rapid tetrazine–trans-cyclooctene/strained-alkene ligation in multi-component assembly. Its value lies in facilitating efficient, chemoselective construction of complex targeted degraders under mild conditions, supporting systematic structure–activity optimization and streamlined synthesis of PROTAC conjugates.
Structure of 1802908-02-6
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Methyltetrazine-PEG4-maleimide is a bifunctional PROTAC linker designed to connect a tetrazine-based recognition handle with a maleimide electrophile for efficient conjugation workflows. Its PEG-based spacer supports favorable solubility and conformational flexibility, which can improve productive ternary complex formation in targeted protein degradation strategies. The molecule is therefore well suited for assembling PROTAC constructs via orthogonal chemistries.
Structure: The linker comprises a methyltetrazine moiety and a maleimide group separated by a poly(ethylene glycol) spacer. It contains aromatic heterocycles, an activated cyclic imide, and ether linkages, with conjugation-capable functional groups. The PEG segment imparts hydrophilicity and flexible spacing, supporting aqueous compatibility.
Reactivity: The methyltetrazine functionality undergoes fast inverse-electron-demand Diels–Alder reactions with strained dienes (commonly trans-cyclooctene derivatives), enabling bioorthogonal assembly under mild conditions. The maleimide reacts with thiols through Michael-type addition, typically using nucleophilic cysteine or reduced thiol-containing partners. Commonly used solvents include aqueous buffers with controlled pH, and reactions are performed to minimize competing thiol oxidation; catalysts are generally not required for either conjugation 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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