Mal-amido-PEG12-TFP ester
Cat No.: BP-501915
Purity: ≥95%
4.5 
Mal-amido-PEG12-TFP ester is a heterobifunctional polyethylene glycol linker designed for PROTAC and targeted protein degradation workflows that require efficient conjugation to lysine-containing proteins or amine-functional ligands. Structurally, it combines a maleimide (Mal) group for selective thiol reactivity, an extended PEG12 chain that provides aqueous solubility and spatial separation, and a tetrafluorophenyl (TFP) ester that reacts with primary amines to form stable amide bonds. In PROTAC assembly, the PEG spacer helps tune the effective distance and flexibility between the two binding/conjugating domains, while the dual-reactive handles enable sequential installation of different molecular components (e.g., coupling a targeting ligand through the TFP ester and attaching a cysteine/thiol-bearing element via the maleimide). This linker is valuable for constructing well-defined conjugates, improving handling in aqueous buffers, and supporting systematic optimization of degrader architectures in mechanistic and cellular studies.
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* For research and manufacturing use only. Not for human or clinical use.
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Mal-amido-PEG12-TFP ester is a heterobifunctional PROTAC linker designed to couple a maleimide-bearing handle to an amine-reactive TFP ester, enabling modular assembly of targeted protein degraders. Its PEG-based spacer supports productive ternary-complex formation by improving solubility and conformational flexibility, while the TFP ester provides efficient electrophilic acylation of nucleophilic groups on ligands or biomolecules. The maleimide moiety serves as a robust conjugation site for thiol-containing partners, making this linker broadly useful for constructing well-defined PROTACs; detailed structural and reactivity considerations are provided below.
Structure: The linker contains a PEG ether chain that imparts hydrophilicity and segmental flexibility, flanked by a maleimide group and a TFP ester. It features an amide linkage connecting the maleimide to the PEG scaffold, with an activated aromatic ester designed for nucleophilic acyl substitution.
Reactivity: The TFP ester reacts with primary amines and other nucleophiles via acyl substitution, typically under mildly basic aqueous or mixed solvent conditions to promote deprotonation while limiting hydrolysis. The maleimide undergoes Michael-type addition with thiols to form stable thioether adducts. For PROTAC assembly, sequential coupling is commonly used: first install the thiol-bearing component, then couple amine-functional ligands, using compatible buffers and avoiding strongly nucleophilic thiols during the TFP ester 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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