Mal-PEG6-NHS
Mal-PEG6-NHS is a heterobifunctional polyethylene glycol (PEG) linker that combines a maleimide group with an N-hydroxysuccinimide (NHS) ester, connected through a PEG chain of moderate length that provides aqueous solubility and reduces nonspecific interactions. The maleimide moiety enables selective, rapid conjugation to thiol-containing biomolecules (for example, cysteine- or engineered thiol-bearing ligands) via a stable thioether linkage, while the NHS ester reacts with primary amines on proteins or amine-functionalized small molecules to form an amide bond. In PROTAC and targeted degradation workflows, this dual-reactive architecture allows researchers to orthogonally install two different binding handles—such as an E3 ligase recruiter and a target-binding ligand—on a single scaffold while maintaining favorable spatial separation for ternary complex formation. Its PEG spacer and chemoselective coupling chemistry make it a practical tool for constructing and optimizing degraders with improved conjugation efficiency and reduced aggregation during assay development.
Structure of 1137109-21-7
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Mal-PEG6-NHS is a heterobifunctional PEG-based linker designed for efficient conjugation in PROTAC workflows. It combines a maleimide handle for selective thiol coupling with an NHS ester that enables amide-bond formation with primary amines, allowing modular assembly of targeted protein degraders. The PEG spacer enhances solubility and flexibility, which can improve bioconjugate accessibility and overall construct performance. Detailed structural and reactivity guidance is provided below.
Structure: The linker contains a maleimide electrophile and an NHS-activated carboxylate, connected through a polyethylene glycol chain that provides hydrophilicity and conformational flexibility. It features reactive carbon–carbon double-bond character within the maleimide and an activated N-hydroxysuccinimide ester suitable for acyl transfer.
Reactivity: Maleimide groups typically undergo rapid Michael-type addition with thiols under mildly basic, aqueous conditions, forming stable thioether linkages. The NHS ester reacts with primary amines to form amide bonds via nucleophilic acyl substitution. In PROTAC synthesis, sequential coupling is commonly used to control chemoselectivity; thiol-containing ligands are introduced after amine coupling, using standard bioconjugation buffers and avoiding thiol contaminants that can quench the NHS ester or maleimide.
* 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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