Mal-amido-PEG8-TFP ester
CAS No.: 1924596-31-5
Cat No.: BP-501442
Purity: ≥95%
4.5 
Mal-amido-PEG8-TFP ester is a heterobifunctional polyethylene glycol (PEG) linker featuring a maleimide “Mal” group for selective thiol conjugation, an amide-linked PEG chain of intermediate length, and a terminal tetrafluorophenyl (TFP) ester for acylation of primary amines. The maleimide moiety reacts with cysteine-containing ligands or engineered proteins via Michael addition, while the TFP ester forms stable amide bonds with lysine residues or amine-bearing small molecules, enabling sequential or orthogonal bioconjugation. In PROTAC and targeted degradation workflows, such linkers are used to connect a ligand that binds an E3 ligase to a second binding moiety (e.g., a target-binding warhead) while maintaining solubility and reducing steric clashes through PEG-mediated spacing. This product is valuable for constructing degraders with improved aqueous handling and tunable linker geometry, facilitating systematic optimization of conjugation efficiency and degradation potency in experimental studies.
Structure of 1924596-31-5
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Mal-amido-PEG8-TFP ester is a heterobifunctional PROTAC linker designed to combine a PEG-based solubilizing segment with a maleimide handle and a TFP ester for efficient electrophilic acyl transfer. Its flexible PEG architecture supports favorable linker conformations and aqueous compatibility, while the TFP ester enables rapid conjugation to nucleophilic groups on targeting ligands. This product is well suited for constructing targeted protein degraders, where the linker geometry and reactivity directly influence productive ternary complex formation; detailed structure and reactivity considerations are provided below.
Structure: The linker incorporates a polyethylene glycol chain bearing an amide linkage, a maleimide group, and a terminal tetrafluorophenyl (TFP) activated ester. It contains maleimide, ester, and amide functional groups, along with ether-rich PEG segments that confer high polarity and water compatibility. The overall structure is flexible, enabling conformational adaptability.
Reactivity: The TFP ester reacts with primary amines, typically via nucleophilic acyl substitution, forming a stable amide bond while releasing the corresponding leaving group. The maleimide can separately undergo thiol-selective Michael addition under mild conditions, while TFP-ester coupling is performed under conditions that maintain amine nucleophilicity and minimize hydrolysis. Suitable solvents include water and polar cosolvents; catalysts are generally unnecessary, but careful control of time and stoichiometry helps preserve ester integrity during PROTAC assembly.
* 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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