Mal-PEG5-NHS ester is a heterobifunctional, PEG-based linker reagent that combines a maleimide group with an N-hydroxysuccinimide (NHS) ester for sequential conjugation. The PEG5 spacer provides a flexible, hydrophilic chain that improves solubility and spatial separation between the two reactive handles, while the maleimide enables selective coupling to thiols (commonly cysteine-containing ligands or reduced thiolated biomolecules) via a stable thioether linkage. In parallel, the NHS ester reacts efficiently with primary amines on targeting ligands (e.g., lysine residues on peptides or proteins) to form an amide bond under standard aqueous conditions. In PROTAC and targeted protein degradation workflows, this linker is used to build modular constructs by first attaching the NHS-reactive moiety to an amine-bearing component and then installing the second component through thiol–maleimide chemistry, thereby enabling controlled assembly of bifunctional degraders. Its value lies in providing robust, chemoselective conjugation chemistry and a tunable spacer that can help optimize ternary-complex formation and experimental reproducibility.
Structure of 1807537-42-3
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Mal-PEG5-NHS ester is a heterobifunctional PEG-based linker designed for efficient conjugation in targeted protein degradation workflows. Its NHS-ester handle enables rapid amide-bond formation with primary amines on ligands or protein-binding modules, while the maleimide functionality supports selective coupling to thiols. This combination supports modular PROTAC assembly with improved solubility and tunable linker length, and
Structure: The molecule contains a maleimide group for thiol-reactive Michael-type addition and an N-hydroxysuccinimide ester for amine acylation. A PEG segment provides flexible, hydrophilic spacing. The linker features an activated carboxylate (NHS ester) and conjugated alkene within the maleimide ring, improving aqueous compatibility.
Reactivity: For PROTAC construction, the NHS ester is typically reacted with primary amines under mildly basic aqueous conditions to form stable amide bonds, after which unreacted NHS ester is commonly quenched or removed. The maleimide can then be coupled to thiols via thiol–maleimide addition, often requiring controlled pH and avoidance of competing thiols. Reaction efficiency depends on reagent stoichiometry, buffer composition, and thiol accessibility.
* 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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