Mal-PEG4-alcohol is a heterobifunctional PEG-based linker featuring a maleimide group and a terminal hydroxyl, enabling stable conjugation and flexible spacing in PROTAC and targeted protein degradation workflows. The maleimide moiety reacts selectively with thiol-containing handles (commonly cysteine residues or thiol-functionalized ligands) via Michael addition, forming a robust thioether linkage that preserves the integrity of the degrader scaffold. The PEG4 chain provides aqueous solubility and conformational flexibility, which can reduce steric interference between the targeting ligand and the recruited E3 ligase binder, thereby improving productive ternary complex formation. In experimental PROTAC design, this linker is useful for modular assembly of conjugates where one component is introduced through thiol chemistry and the other can be functionalized from the hydroxyl terminus for subsequent coupling. Overall, it supports systematic optimization of linker length and attachment geometry for more reliable targeted degradation studies.
Structure of 1421933-37-0
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Mal-PEG4-alcohol is a PEG-based, maleimide-functional linker designed for efficient conjugation in targeted protein degradation workflows. Its maleimide handle enables selective coupling to thiol-bearing ligands, while the PEG spacer promotes solubility and favorable linker flexibility in PROTAC architectures. This product is commonly used to assemble degraders by connecting a thiol-reactive warhead to a partner ligand through a stable thioether linkage. The following points describe the structure and reactivity characteristics in detail.
Structure: The linker combines a maleimide electrophile with a polyethylene glycol chain terminating in an alcohol. It contains an alkene within the maleimide ring and ether linkages along the PEG segment, providing a polar, flexible scaffold that supports aqueous compatibility and controlled spatial presentation of attached ligands.
Reactivity: Maleimide groups undergo thiol–maleimide Michael-type addition to form a thioether, typically under mildly basic conditions that favor thiolate formation while minimizing maleimide hydrolysis. Suitable thiol sources include cysteine-containing ligands or reduced thiol reagents. Reactions are commonly performed in aqueous or mixed aqueous/organic solvents, with careful control of pH and temperature to preserve maleimide reactivity and maintain linker integrity during PROTAC 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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