Acid-PEG3-NHS ester
CAS No.: 1835759-79-9
Cat No.: BP-501559
Purity: ≥95%
4.5 
Acid-PEG3-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker featuring a terminal N-hydroxysuccinimide (NHS) ester for efficient amide-bond formation and a carboxylic acid handle that provides controlled attachment chemistry for PROTAC and related targeted protein degradation constructs. Structurally, it consists of a short PEG chain with an NHS-activated carboxylate equivalent, offering a flexible, hydrophilic spacer that can reduce steric interference between the ligand-binding moiety and the E3 ligase recruiter. In PROTAC design, the NHS ester enables rapid conjugation to primary amines present on proteins, peptides, or amine-functionalized small-molecule ligands, while the acid functionality supports further coupling strategies or downstream derivatization. This linker’s balance of flexibility and aqueous solubility is valuable for optimizing linker length, maintaining productive ternary complex formation, and improving synthetic modularity for systematic structure–activity studies in targeted degradation research.
Structure of 1835759-79-9
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Acid-PEG3-NHS ester is a PEG-based activated carboxylic acid linker designed for efficient conjugation in targeted protein degradation workflows. Its NHS ester functionality enables rapid formation of stable amide bonds with primary amines, facilitating the assembly of PROTACs and related bifunctional degraders. The flexible PEG spacer can help tune solubility and spatial presentation of warheads, supporting reliable linker installation. Detailed structural and reactivity considerations are provided below.
Structure: The molecule comprises a short polyethylene glycol spacer terminating in a carboxylic acid and an N-hydroxysuccinimide ester. It contains an activated ester linkage, ether-rich PEG segments, and an amide-forming electrophilic carbonyl. The PEG segment imparts hydrophilicity and conformational flexibility, while the NHS ester increases acyl transfer reactivity.
Reactivity: The NHS ester reacts with primary amines to form amide bonds via nucleophilic acyl substitution. For PROTAC synthesis, amine-bearing ligands are typically coupled under mildly basic conditions to maintain amine nucleophilicity while minimizing hydrolysis of the activated ester. Common solvents include aqueous-organic mixtures or polar aprotic media compatible with NHS chemistry. No specialized catalysts are generally required; careful control of water content and reaction time helps preserve coupling efficiency.
* 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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