Bis(NHS)PEG5
Bis(NHS)PEG5 is a bifunctional polyethylene glycol (PEG) linker bearing two N-hydroxysuccinimide (NHS) ester termini, enabling efficient, chemoselective conjugation to primary amines on PROTAC-relevant ligands or other targeting modules. Structurally, it consists of a PEG5 chain that provides aqueous solubility and conformational flexibility, while the NHS groups serve as activated acylating agents that form stable amide bonds upon reaction with lysine residues or N-terminal amino groups. In PROTAC design, this type of linker is used to connect components such as a ligand for an E3 ligase to a ligand for the target protein, allowing spatial separation that can improve productive ternary complex formation and overall degradation potency. Its utility in targeted protein degradation research stems from the ability to tune linker length and reduce aggregation, facilitating reproducible synthesis of conjugates for downstream biochemical and cellular evaluation.
Structure of 756526-03-1
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Bis(NHS)PEG5 is a bifunctional PEG-based linker designed for efficient conjugation in PROTAC workflows, enabling the connection of two targeting or reactive modules through NHS-ester chemistry. Its flexible polyethylene glycol scaffold supports favorable solubility and linker dynamics, which can improve the practical assembly of degraders. The subsequent points describe its structural features and the experimental considerations for PROTAC construction in detail.
Structure: The linker contains two N-hydroxysuccinimide (NHS) ester groups attached to a polyethylene glycol chain, providing two electrophilic acyl sites. It features stable amide-forming functional groups, ether-rich PEG segments, and polar, water-compatible character that supports conjugation and solubility.
Reactivity: Bis(NHS)PEG5 is typically coupled to primary amines on ligands (e.g., lysine residues or amine-bearing handles) via nucleophilic acyl substitution, forming stable amide bonds while releasing NHS. Suitable conditions generally use mildly basic aqueous buffers or organic/aqueous mixtures to promote amine nucleophilicity while maintaining NHS-ester integrity. Reactions are commonly performed at controlled pH, with careful stoichiometry to manage mono- versus bis-conjugation, and with quenching or purification to remove unreacted NHS esters.
* 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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