m-PEG3-phosphonic acid
CAS No.: 96962-42-4
Cat No.: BP-501137
4.5 
m-PEG3-phosphonic acid is a short, linear polyethylene glycol (PEG) linker bearing a methoxy cap at one terminus and a phosphonic acid at the other, providing a polar PEG-based building block for PROTAC and targeted degradation workflows. The PEG3 chain supplies hydrophilicity and conformational flexibility, helping to reduce steric clashes between the ligand-binding moieties and the recruited E3 ligase or target-binding domain. The phosphonic acid group mainly contributes acidity, polarity, and coordination capability and is not a standard amide- or click-type covalent coupling handle. In PROTAC design, this combination supports controlled spatial separation and improved aqueous compatibility of multi-domain constructs, which can be critical for maintaining binding competence and promoting efficient ternary-complex formation. As a compact, functionalized PEG linker, it is valuable for constructing and optimizing degraders where linker length, polarity, and attachment geometry strongly influence degradation potency and selectivity.
Structure of 96962-42-4
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m-PEG3-phosphonic acid is a PEG-based phosphonic acid linker designed to support PROTAC assembly by providing a hydrophilic, flexible spacer and a chemically addressable phosphonate handle. Its combination of ether-rich chain mobility and strong phosphate-like binding motifs can improve solubility and facilitate stable conjugation strategies in targeted protein degradation workflows. The following sections describe the linker’s structure and practical reactivity considerations in detail below.
Structure: The linker contains a methoxy-terminated poly(ethylene glycol) segment connected to a phosphonic acid functionality. It features ether linkages within the PEG chain and a phosphonate group capable of forming hydrogen bonds and ionic interactions. Overall, it is expected to be water-compatible and conformationally flexible.
Reactivity: The phosphonic acid group can be used for PROTAC construction via phosphonate activation or coupling chemistries commonly employed for phosphonate-containing linkers. Typical approaches involve converting the acid to a more reactive intermediate under mild, moisture-controlled conditions, followed by nucleophilic substitution or ester/amide formation with compatible partner functional groups. Solvent systems that dissolve both coupling partners and allow controlled activation are generally selected, and base or coupling reagents may be required depending on the chosen synthetic route.
* 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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