Mal-PEG8-NHS ester
Mal-PEG8-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker featuring a maleimide group and an N-hydroxysuccinimide (NHS) ester. The PEG chain length provides a flexible, hydrophilic spacer that reduces steric hindrance and helps preserve the binding activity of conjugated partners. In PROTAC and related targeted degradation constructs, the maleimide moiety enables selective thioether formation with cysteine-containing ligands or engineered proteins, while the NHS ester reacts efficiently with primary amines on peptides, lysine residues, or amine-functionalized warheads to form stable amide linkages. This dual-reactivity supports modular assembly of bifunctional degraders by sequentially coupling one component through the NHS ester and the other through the maleimide, enabling controlled orientation and improved conjugate solubility. The product is therefore valuable for preparing research-grade PROTAC linkers and optimizing degradation reagents where linker flexibility and conjugation specificity are critical.
Structure of 2055033-05-9
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* For research and manufacturing use only. Not for human or clinical use.
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Mal-PEG8-NHS ester is a PEG-based bifunctional linker designed for constructing PROTACs and related targeted protein degradation conjugates. It couples a maleimide handle with an N-hydroxysuccinimide (NHS) ester to enable sequential attachment to thiol- and amine-bearing ligands under mild aqueous conditions. The flexible PEG spacer can improve solubility and reduce steric constraints, supporting efficient formation of heterobifunctional degraders. Detailed structural and reactivity considerations are provided below.
Structure: The molecule contains a maleimide moiety for thiol conjugation and an NHS ester for amine acylation, connected through a polyethylene glycol (PEG) chain. It features an activated succinimidyl carbonate-like leaving group and a conjugated maleimide double bond, yielding water-compatible, flexible, and bioconjugation-ready properties.
Reactivity: For PROTAC assembly, the NHS ester typically reacts with primary amines on targeting ligands to form stable amide bonds, commonly using buffered aqueous conditions that preserve NHS reactivity. The maleimide then undergoes Michael-type addition with accessible thiols to form thioether linkages. Catalysis is generally not required; select solvents and pH ranges that maintain maleimide stability and minimize hydrolysis, while using thiol-protecting strategies when sequential coupling is desired.
* 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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