Acid-PEG4-S-S-PEG4-acid
CAS No.: 2055015-40-0
Cat No.: BP-501142
Purity: ≥95%
4.5 
Acid-PEG4-S-S-PEG4-acid is a symmetric homobifunctional PEG-based diacid linker featuring two terminal carboxylic acid groups connected through a disulfide (S–S) core and two short PEG4 segments. The disulfide linkage provides a redox-responsive handle that can be cleaved under intracellular reducing conditions, enabling controlled release or rearrangement of conjugates, while the PEG chains improve aqueous solubility and reduce nonspecific adsorption. In PROTAC design, this scaffold is well suited for connecting two PROTAC-relevant modules—such as a ligand for an E3 ligase and a ligand for the target protein—by providing reactive sites for amide coupling or other carboxyl-derivatization chemistries. Its redox-cleavable nature can help tune the effective lifetime and intracellular processing of the assembled degrader, supporting studies on degradation kinetics, linker stability, and structure–activity relationships.
Structure of 2055015-40-0
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This Acid-PEG4-S-S-PEG4-acid linker is designed to connect two PROTAC-binding modules through a reducible disulfide motif embedded in polyethylene glycol (PEG) arms. Its flexible PEG architecture supports productive ternary complex formation, while the S–S linkage enables redox-responsive cleavage under intracellular conditions. The result is a versatile linker platform for constructing targeted protein degraders, with detailed structural and synthetic considerations provided below.
Structure: The linker contains two PEG4 segments terminated with carboxylic acid groups, connected by a central disulfide bond. Its ether-rich PEG framework provides conformational flexibility, while the disulfide introduces a redox-labile S–S linkage. Overall, the molecule is polar, water-compatible, and suitable for amide-forming conjugation strategies.
Reactivity: PROTAC assembly commonly employs carboxylic acid activation followed by coupling to complementary amine or hydrazide/amine-bearing warheads using standard peptide-coupling chemistries. The disulfide is generally preserved during coupling by avoiding strongly reducing conditions. Typical approaches use activating agents and base in polar aprotic or aqueous/organic mixtures, enabling formation of stable amide bonds while retaining the redox-sensitive S–S motif for downstream cleavage-driven degradation.
* 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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