Azido-PEG24-NHS ester
CAS No.: 2375600-46-5
Cat No.: BP-502130
4.5 
Azido-PEG24-NHS ester is a heterobifunctional polyethylene glycol linker featuring a terminal azide group for bioorthogonal conjugation and an N-hydroxysuccinimide (NHS) ester for efficient acylation of primary amines on proteins or peptides. The extended PEG chain provides a flexible, hydrophilic spacer that reduces steric interference and helps preserve the binding and degradation-relevant conformations of PROTAC components. In PROTAC design, this linker enables modular assembly by first coupling the NHS ester to an amine-bearing targeting ligand or carrier, then using the azide handle to attach the complementary moiety via azide–alkyne cycloaddition (Cu-free or Cu-mediated, depending on conditions) or related click chemistries. Its long, solvent-swelling backbone is particularly valuable for improving effective molarity and tuning linker length to optimize ternary complex formation and targeted protein degradation performance.
Structure of 2375600-46-5
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Azido-PEG24-NHS ester is a heterobifunctional PEG-based linker designed for modular PROTAC construction, enabling efficient conjugation to ligand scaffolds and subsequent installation of a bioorthogonal azide handle. Its PEG spacer promotes favorable solubility and conformational flexibility, which can improve productive ternary complex formation. The azide functionality supports orthogonal click-type coupling strategies, while the NHS ester enables rapid amide bond formation under mild conditions. Detailed structural and reactivity guidance is provided below.
Structure: The molecule comprises a polyethylene glycol chain terminated by an azide group and an N-hydroxysuccinimide ester. It contains an NHS-activated carboxyl derivative for nucleophilic acyl substitution and an azide suitable for copper-free or copper-mediated cycloaddition chemistry. The PEG segment provides hydrophilicity and flexible spacing.
Reactivity: The NHS ester reacts with primary amines to form stable amide linkages via nucleophilic acyl substitution, typically under buffered, mildly basic aqueous conditions. After amide formation, the remaining azide can be used for strain-promoted or copper-catalyzed azide–alkyne cycloaddition to connect the second PROTAC component. Common solvents include aqueous buffers with compatible co-solvents, and reaction design should minimize azide reduction and NHS hydrolysis.
* 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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