Mal-DPEG4-NHS
CAS No.: 756525-99-2
Cat No.: BP-501569
Purity: ≥98%
4.5 
Mal-DPEG4-NHS is a bifunctional, PEG-based linker designed for PROTAC and targeted protein degradation workflows, combining a maleimide electrophile with an NHS ester for orthogonal bioconjugation. The PEG4 segment provides a flexible, hydrophilic spacer that can reduce steric interference and help maintain productive geometry between the two PROTAC arms. In practical assembly, the maleimide group enables selective coupling to thiol-containing ligands (for example, cysteine- or thiol-derivatized warheads), while the NHS ester reacts with primary amines to install the complementary binding or targeting component. This dual-reactivity architecture supports modular synthesis of degraders by allowing sequential attachment under controlled conditions, improving reproducibility and enabling rapid generation of structure–activity variants. As a result, Mal-DPEG4-NHS is a valuable reagent for researchers optimizing linker length, flexibility, and conjugation strategy to enhance ternary complex formation and degradation efficiency in targeted protein degradation studies.
Structure of 756525-99-2
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Mal-DPEG4-NHS is a heterobifunctional PROTAC linker designed to connect an amine-bearing targeting ligand to a compatible protein-binding partner through an NHS ester handle. Its polyethylene glycol–based spacing supports favorable solubility and reduces steric constraints, which can improve linker accessibility and overall conjugation efficiency. The subsequent points describe its structural features and practical reactivity for constructing PROTACs using this NHS-activated intermediate.
Structure: Mal-DPEG4-NHS contains a maleimide moiety paired with a terminal N-hydroxysuccinimide ester on a DPEG4 polyethylene glycol spacer. It features an NHS-activated carboxylate for acyl transfer and a maleimide alkene suited for selective thio-Michael addition, with ether-rich flexibility that enhances aqueous compatibility.
Reactivity: The NHS ester reacts with primary amines to form stable amide bonds under mildly basic aqueous conditions, typically using buffered solvents that preserve maleimide integrity. The maleimide group undergoes thio-Michael addition with thiols (such as cysteine residues or thiol-containing ligands) to yield a thioether linkage. For sequential assembly, amine coupling is commonly performed first, followed by controlled thiol addition, with careful avoidance of competing thiols and strong nucleophiles.
* 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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