SPDP-PEG24-NHS ester
SPDP-PEG24-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker bearing an NHS ester for amide coupling to primary amines and a cleavable pyridyl disulfide (SPDP) group for thiol-mediated conjugation. Structurally, it combines a long, flexible PEG chain that increases hydrophilicity and spacing between conjugated partners with a disulfide linkage that can be reduced in intracellular or reducing microenvironments, enabling controlled release or rearrangement of the conjugate. In PROTAC and targeted degradation workflows, this linker is used to connect a ligand-bearing amine to the NHS-activated end, while the SPDP disulfide can react with thiols introduced on the other component (e.g., via cysteine residues or thiol-modified handles), thereby bringing the two binding moieties into proximity. Its value lies in facilitating modular assembly, improving solubility, and tuning effective linker length and conjugation chemistry to support systematic optimization of ternary-complex formation and degradation potency.
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* For research and manufacturing use only. Not for human or clinical use.
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SPDP-PEG24-NHS ester is a PEG-based heterobifunctional linker designed for conjugation workflows commonly used in PROTAC construction. It provides an NHS-activated ester for efficient coupling to primary amines on targeting ligands, while retaining a thiol-reactive disulfide functionality for subsequent formation of a reversible thio-disulfide linkage. This combination enables modular assembly, tunable spacing, and compatibility with aqueous, bioconjugation-friendly conditions; detailed structural and reactivity considerations are provided below.
Structure: The linker contains a poly(ethylene glycol) chain that imparts hydrophilicity and conformational flexibility, terminated by an NHS ester for acyl transfer to amines and a pyridyl disulfide moiety for thiol/disulfide exchange. It features ester and disulfide bonds, with a stable PEG backbone supporting solubility.
Reactivity: The NHS ester reacts with primary amines via nucleophilic acyl substitution to form an amide bond under mildly basic aqueous conditions, typically in the presence of controlled pH and minimal competing nucleophiles. The disulfide reacts through thiol–disulfide exchange, often using a reducing or thiol-containing partner to generate a reactive intermediate for linkage. Common solvents include buffered aqueous media; catalysts are generally not required, but reaction order and purification are critical for clean PROTAC assembly.
* 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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