Acid-PEG25-NHS ester
Acid-PEG25-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker featuring a terminal carboxylic acid (“acid”) and an N-hydroxysuccinimide (NHS) ester for amide-bond formation. Structurally, it provides a long, flexible PEG chain that can spatially separate a targeting ligand from an E3-ligase-binding moiety, while the NHS ester serves as a reactive handle to conjugate to primary amines on proteins, peptides, or small-molecule intermediates under standard aqueous coupling conditions. In PROTAC and targeted protein degradation workflows, such linkers are commonly used to tune effective distance, reduce steric interference, and improve solubility and handling of conjugates, thereby facilitating productive ternary complex formation between the recruited target and the ligase. The extended PEG architecture can also help mitigate nonspecific aggregation during synthesis and downstream assays, making this reagent a practical component for constructing and optimizing degradation-inducing conjugates.
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* For research and manufacturing use only. Not for human or clinical use.
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Acid-PEG25-NHS ester is a PEG-based PROTAC linker intermediate designed to connect a carboxylic acid functional group to an amine-reactive NHS ester handle. Its flexible, hydrophilic PEG segment helps improve solubility and can reduce steric constraints during conjugation steps that are central to PROTAC assembly. The NHS ester enables efficient coupling to suitable nucleophiles on targeting ligands, while the terminal acid provides a complementary functional group for subsequent linkage strategies. Detailed structural and reactivity considerations are provided below.
Structure: This linker is built on a polyethylene glycol (PEG) backbone terminating in an activated N-hydroxysuccinimide ester and a carboxylic acid functionality. It contains ether linkages along the PEG chain and an NHS carbonate-like acyl linkage, providing a flexible, water-compatible spacer with an electrophilic ester center.
Reactivity: The NHS ester reacts with primary amines and other suitable nucleophiles under mild, anhydrous-to-semi-aqueous conditions to form stable amide bonds, typically via nucleophilic acyl substitution. Common approaches use amine-containing coupling partners in buffered organic/aqueous solvent systems, with pH controlled to favor NHS activation while minimizing hydrolysis. No special catalysts are generally required; careful exclusion of water and timely quenching are important to preserve reactivity.
* 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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