SPDP-PEG4-COOH
CAS No.: 581065-97-6
Cat No.: BP-501510
Purity: ≥95%
4.5 
SPDP-PEG4-COOH is a heterobifunctional polyethylene glycol linker designed for constructing PROTACs and other targeted conjugates. Structurally, it incorporates an NHS-activated disulfide (SPDP) group for covalent attachment to primary amines on one PROTAC module, together with a terminal carboxylic acid that can be used for amide coupling to a second module bearing an appropriate amine or activated ester. The PEG4 segment provides a short, flexible hydrophilic spacer that can reduce steric interference and improve the effective proximity and orientation of the recruited binding ligands, which is critical for efficient ternary complex formation and subsequent ubiquitin–proteasome–mediated degradation. In PROTAC workflows, the disulfide linkage enables intracellularly relevant thiol exchange, allowing controlled transfer of the conjugate connection between partners. This linker is valuable for assembling well-defined, modular degraders and for optimizing linker length and physicochemical properties to support robust degradation studies.
Structure of 581065-97-6
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SPDP-PEG4-COOH is a polyethylene glycol-based bifunctional linker designed to enable efficient conjugation of affinity ligands in PROTAC construction. Its activated disulfide functionality supports thiol-mediated coupling, while the terminal carboxyl group provides a handle for subsequent amide-bond formation. This combination facilitates modular assembly of targeted protein degraders with controlled linker length and improved solubility, and the following sections describe the structure and practical reactivity considerations in detail.
Structure: The linker contains a PEG4 ether chain that imparts flexibility and hydrophilicity, a terminal carboxylic acid for acyl coupling, and an activated disulfide (SPDP) electrophile for thiol capture. It features ether and amide-forming functional groups, with a stable, conjugation-ready scaffold.
Reactivity: SPDP-type activated disulfides react with primary thiols or cysteine-containing ligands under thiol–disulfide exchange, typically in aqueous or mixed aqueous buffers at controlled pH to favor nucleophilic attack. The resulting thio-disulfide intermediate can be carried forward for PROTAC assembly, while the carboxyl group is suitable for amide coupling using standard coupling reagents in compatible solvents.
* 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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