Methyltetrazine-PEG13-NHS ester
Cat No.: BP-501893
4.5 
Methyltetrazine-PEG13-NHS ester is a heterobifunctional PEG-based linker that combines a methyltetrazine reactive handle with an NHS ester for amide-bond formation. Structurally, it features a long, flexible polyethylene glycol chain that spaces two conjugation sites and can reduce steric hindrance and nonspecific interactions. In PROTAC and targeted degradation workflows, the NHS ester enables coupling to primary amines on ligands such as lysine-bearing targeting moieties or engineered protein-binding components, forming a stable amide linkage. The methyltetrazine group serves as a bioorthogonal partner for rapid inverse-electron-demand Diels–Alder reactions with strained alkenes (commonly trans-cyclooctene or BCN-type groups), allowing modular assembly of multi-component degraders under mild conditions. This linker is valuable for constructing well-defined, distance-tuned conjugates, improving the efficiency and controllability of ternary-complex formation and enabling systematic optimization of linker length and attachment chemistry in targeted protein degradation research.
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* For research and manufacturing use only. Not for human or clinical use.
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Methyltetrazine-PEG13-NHS ester is a bifunctional PROTAC linker designed to support efficient conjugation workflows and modular assembly of targeted protein degraders. The methyltetrazine handle enables bioorthogonal reactivity with suitable strained dienes, while the NHS ester provides a robust route for amide-bond formation with primary amines on ligands. Together, these features facilitate controlled linker installation, improved synthetic flexibility, and reproducible construct preparation. The detailed structural and reactivity characteristics are provided below.
Structure: The linker comprises a methyltetrazine moiety connected to a polyethylene glycol spacer terminating in an N-hydroxysuccinimide ester. It contains heteroaromatic nitrogen-rich chemistry in the tetrazine unit, ether-rich PEG segments, and an activated carboxylate functionality suited for nucleophilic acyl substitution.
Reactivity: The NHS ester reacts with primary amines under mild, aqueous-compatible conditions to form stable amide bonds via nucleophilic acyl substitution, typically using buffering systems that maintain the amine in a reactive form. The methyltetrazine group undergoes fast inverse-electron-demand Diels–Alder ligation with strained dienes, enabling modular assembly. Solvent choice and pH should preserve both the amine-reactive NHS ester and the tetrazine reactivity during sequential conjugation steps.
* 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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