Bis-MAL-PEG4-PEG12-Lysine-Tris(PEG24-COOH)
Bis-MAL-PEG4-PEG12-Lysine-Tris(PEG24-COOH) is a branched, multiarm PEG-based linker built around a lysine core that provides a defined scaffold for PROTAC assembly. It contains two maleimide termini for thiol–maleimide conjugation, enabling attachment to cysteine-bearing ligands or engineered protein-binding moieties, while the remaining lysine-linked arms terminate in carboxyl groups that can be used for further derivatization or formulation. The extended PEG segments (short PEG4 and longer PEG12 spacers plus three PEG24–carboxyl arms) impart high aqueous solubility, reduce nonspecific hydrophobic interactions, and provide conformational flexibility that helps maintain productive geometry between the target-binding ligand and the E3-recruiting component. In targeted protein degradation research, such PEGylated, multi-functional linkers are valuable for tuning linker length and branching, improving conjugation efficiency, and supporting systematic structure–activity relationship studies across PROTAC constructs.
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* For research and manufacturing use only. Not for human or clinical use.
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This PROTAC linker is designed to provide a flexible, water-compatible scaffold that connects two binding elements while supporting productive ternary complex formation. Its extended PEG architecture helps tune solubility and spatial presentation of ligands, which can improve degradation efficiency in targeted protein degradation workflows. The structure and reactivity considerations for assembling PROTAC constructs are described in detail below.
Structure: The linker contains a lysine core bearing multiple PEG substituents, including MAL-terminated and carboxyl-terminated PEG arms. It is characterized by ether-rich PEG segments, amide linkages to the lysine scaffold, and terminal functional groups suitable for conjugation. Overall, it is highly hydrophilic and conformationally flexible, favoring aqueous handling.
Reactivity: MAL (maleimide) functionalities enable thiol-selective conjugation via Michael-type addition with cysteine-containing ligands or thiol-bearing intermediates under mildly basic, aqueous conditions. Carboxyl-terminated PEG arms can be activated for amide bond formation using standard coupling chemistries, typically employing carbodiimide-based activation with an appropriate activator and base in compatible solvents. The flexible PEG environment generally supports efficient coupling while minimizing aggregation during synthesis.
* 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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