SPDP-PEG8-COOH
CAS No.: 1334177-96-6
Cat No.: BP-501056
Purity: ≥95%
4.5 
SPDP-PEG8-COOH is a heterobifunctional PEG linker bearing a thiol-reactive pyridyldithiol (SPDP) group and a terminal carboxylic acid, providing a flexible, water-soluble spacer of approximately eight ethylene glycol units. The pyridyl disulfide moiety undergoes disulfide exchange with free thiols on targeting ligands or other PROTAC components, while the terminal carboxyl group offers a convenient handle for amide coupling to introduce the linker into larger constructs. In PROTAC design, this type of PEG spacer helps tune the effective distance and conformational freedom between the ligand-binding domains, which can improve cooperative engagement of the target protein and the E3 ligase recruiter and thereby affect ternary complex stability. The carboxyl functionality also supports standardized synthetic workflows for building modular, aqueous PROTACs for targeted protein degradation studies, facilitating systematic optimization of linker length and attachment chemistry.
Structure of 1334177-96-6
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SPDP-PEG8-COOH is a heterobifunctional PEG-based linker designed for building PROTACs and related targeted protein degradation constructs. Its pyridyl disulfide functionality enables thiol–disulfide exchange with thiol-containing ligands, while the terminal carboxylic acid supports subsequent coupling or handle installation. The PEG spacer promotes favorable solubility and linker flexibility, which can improve productive ternary complex formation. Detailed structural and reactivity considerations are provided below.
Structure: The linker contains a PEG chain providing hydrophilicity and conformational flexibility, coupled to a carboxylic acid for further derivatization. A disulfide-containing “SPDP” motif provides a reducible linkage element. Multiple ether linkages support hydrophilicity, while the pyridyl disulfide provides a thiol-reactive exchange handle.
Reactivity: Conjugation at the pyridyl disulfide typically proceeds by thiol–disulfide exchange with a thiol-bearing partner under mild conditions, while retaining the disulfide linkage in the resulting conjugate. For PROTAC assembly, the carboxyl group is commonly used for carbodiimide-mediated coupling or activated ester formation with amine-bearing partners. Reaction progress is monitored by standard analytical methods, and disulfide integrity is maintained by avoiding strongly reducing environments until the intended activation step.
* 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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