Methyltetrazine-PEG24-NHS ester
Cat No.: BP-501758
4.5 
Methyltetrazine-PEG24-NHS ester is a heterobifunctional PEG-based linker that combines a methyltetrazine bioorthogonal handle with an N-hydroxysuccinimide (NHS) ester for efficient conjugation to primary amines. Structurally, it features a long, flexible polyethylene glycol chain that spatially separates the reactive termini, improving accessibility and reducing steric interference during PROTAC assembly. In targeted degradation workflows, the methyltetrazine group enables rapid tetrazine–trans-cyclooctene (TCO) ligation, allowing researchers to connect two PROTAC components under mild conditions, while the NHS ester can be used to functionalize lysine-containing ligands, antibody fragments, or amine-bearing warheads prior to coupling. This linker’s combination of orthogonal reactivity and extended hydrophilicity makes it valuable for constructing modular, well-tolerated PROTACs and for tuning effective distance and conjugate stability in cellular degradation experiments.
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* For research and manufacturing use only. Not for human or clinical use.
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Methyltetrazine-PEG24-NHS ester is a bifunctional PROTAC linker designed to combine a methyl-tetrazine bioorthogonal handle with an NHS-ester for efficient amide-bond formation to install targeting ligands. Its PEG-based spacer provides a flexible, hydrophilic architecture for modular conjugation workflows. The following points describe the structure and the practical reactivity considerations for assembling PROTAC constructs using this linker.
Structure: The molecule contains a methyl-substituted tetrazine moiety linked through a polyethylene glycol spacer to an activated N-hydroxysuccinimide ester. It features stable ether linkages within the PEG chain, an electrophilic NHS ester for acyl substitution, and a conjugated tetrazine ring suitable for inverse-electron-demand cycloaddition.
Reactivity: The NHS ester reacts with primary amines on targeting ligands under mildly basic aqueous or mixed solvent conditions to form stable amide bonds, typically requiring fresh preparation and controlled pH to limit hydrolysis. The tetrazine group can undergo bioorthogonal cycloaddition with appropriate strained dienophiles (e.g., trans-cyclooctenes) via an inverse-electron-demand mechanism. Use compatible buffers and avoid nucleophiles that quench the activated ester.
* 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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