Methyltetrazine-PEG5-alkyne
CAS No.: 1802907-97-6
Cat No.: BP-501296
Purity: 95%
4.5 
Methyltetrazine-PEG5-alkyne is a heterobifunctional PROTAC linker featuring a methyltetrazine moiety conjugated to a five-unit polyethylene glycol (PEG) chain terminating in an alkynyl group. The methyltetrazine handle is designed for rapid, bioorthogonal inverse-electron-demand Diels–Alder ligation with strained trans-cyclooctene or bicyclononyne partners, enabling efficient assembly of PROTACs under mild conditions while minimizing off-target reactions. The PEG spacer provides conformational flexibility and aqueous solubility, helping to reduce steric interference between the targeting ligand and the E3 ligase recruiter during ternary complex formation. The terminal alkyne enables orthogonal functionalization, such as subsequent click-type derivatization or surface/bioconjugation workflows, facilitating modular PROTAC synthesis and optimization. This linker is valuable for researchers seeking reliable, modular conjugation strategies to generate targeted protein degraders with tunable geometry and improved synthetic control.
Structure of 1802907-97-6
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Methyltetrazine-PEG5-alkyne is a bifunctional PROTAC linker designed to integrate a tetrazine handle for rapid IEDDA conjugation and a terminal alkyne for separate CuAAC coupling to targeting or scaffold components. Its PEG-based spacer supports favorable solubility and conformational flexibility, which can improve effective ternary complex formation in targeted protein degradation workflows. The points below describe the linker’s structure and practical reactivity considerations for constructing PROTACs in a stepwise manner.
Structure: The linker combines a methyltetrazine moiety with an alkynyl terminus and a poly(ethylene glycol) spacer. It contains aromatic heterocycles, ether linkages within the PEG chain, and a terminal carbon–carbon triple bond, yielding a flexible, water-compatible scaffold suitable for conjugation chemistry.
Reactivity: The methyltetrazine group undergoes rapid inverse electron-demand Diels–Alder (IEDDA) reaction with strained dienophiles such as trans-cyclooctene (TCO), while the unstrained terminal alkyne is used separately for CuAAC with azides. For PROTAC assembly, the tetrazine and terminal alkyne should be treated as orthogonal handles: use a strained dienophile partner for IEDDA at the tetrazine and an azide partner with copper catalysis for CuAAC at the terminal alkyne. Reaction progress is commonly monitored by analytical methods such as LC-MS.
* 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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