Mal-PEG8-NHS
Mal-PEG8-NHS is a heterobifunctional polyethylene glycol linker featuring a maleimide group and an N-hydroxysuccinimide (NHS) ester separated by a PEG chain of intermediate length. The maleimide moiety enables selective conjugation to thiol-containing residues (for example, cysteines) via a Michael-type addition, while the NHS ester reacts efficiently with primary amines on proteins or peptides to form stable amide bonds. In PROTAC and targeted degradation workflows, this dual-reactive architecture allows researchers to orthogonally connect two different molecular components—such as an amine-bearing ligand and a thiol-functionalized partner—while the PEG spacer provides aqueous solubility and can reduce steric constraints that otherwise impair formation of the ternary complex. As a versatile, experimentally used PEG linker, Mal-PEG8-NHS is valuable for constructing well-defined conjugates and for optimizing linker length and attachment chemistry in targeted protein degradation studies.
Structure of 756525-93-6
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Mal-PEG8-NHS is a heterobifunctional PEG-based linker designed for efficient PROTAC assembly, combining a maleimide handle for selective thiol conjugation with an NHS ester for acylation of primary amines. Its flexible polyethylene glycol spacer supports productive ternary complex formation and improves solubility and bioconjugation compatibility. The linker enables modular construction of targeted protein degraders, and the following sections describe its structural features and practical reactivity for experimental workflows.
Structure: Mal-PEG8-NHS features a maleimide electrophile linked through a polyethylene glycol chain to an N-hydroxysuccinimide ester. The molecule contains amide and ester functionalities, an activated NHS carbonate-like leaving group, and a conjugated maleimide double bond. Its PEG backbone imparts high hydrophilicity and conformational flexibility.
Reactivity: The NHS ester reacts with primary amines to form stable amide bonds under mildly basic aqueous conditions, typically using buffered media compatible with protein functionalization. The maleimide undergoes Michael-type addition with accessible thiols (for example, cysteine or reduced thiol groups) to yield a thioether linkage. For PROTAC synthesis, sequential conjugation is commonly employed, with careful control of pH and thiol availability to minimize side reactions such as hydrolysis or premature crosslinking.
* 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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