BCN-PEG4-NHS ester
Cat No.: BP-501977
4.5 
BCN-PEG4-NHS ester is a polyethylene glycol (PEG) linker reagent featuring a BCN (bicyclononyne) strained-alkyne handle conjugated to a four-unit PEG chain terminated with an N-hydroxysuccinimide (NHS) ester. Structurally, the PEG segment provides aqueous solubility and flexible spacing, while the NHS ester enables efficient, amine-reactive coupling to lysine residues on proteins or to primary amines on peptides, yielding stable amide bonds. In PROTAC and targeted protein degradation workflows, this linker is used to install a BCN functionality onto the target-binding or E3-ligase–binding component, which can then undergo rapid strain-promoted azide–alkyne cycloaddition with a complementary azide partner under copper-free conditions. This orthogonal bioorthogonal conjugation strategy supports modular assembly of multi-component degraders, improves conjugate homogeneity, and facilitates systematic optimization of linker length and attachment chemistry for evaluating degradation potency and selectivity.
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* For research and manufacturing use only. Not for human or clinical use.
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BCN-PEG4-NHS ester is a PEG-based bifunctional linker designed for efficient conjugation in PROTAC workflows. Its NHS ester handle enables robust amide-bond formation with primary amines, while the BCN (bicyclononyne) moiety supports bioorthogonal click chemistry for installing the linker onto compatible partners under mild conditions. This combination offers reliable coupling efficiency, improved solubility, and modular assembly of targeted degradation constructs. Detailed structural and reactivity considerations are provided below.
Structure: The linker comprises a BCN functional group connected through a polyethylene glycol spacer to an N-hydroxysuccinimide ester. It contains an activated carboxylate (NHS ester) for acyl transfer and ether-rich PEG segments that confer flexibility and enhanced hydrophilicity. The BCN unit provides a strained alkyne suitable for click-type reactions.
Reactivity: The NHS ester reacts with primary amines to form stable amide bonds via nucleophilic acyl substitution. Suitable conditions typically use mildly basic aqueous buffer or organic–aqueous mixtures to maintain amine nucleophilicity while minimizing hydrolysis of the activated ester. The BCN component is compatible with strain-promoted cycloaddition approaches, proceeding without added metal catalysts. Fresh reagent preparation and controlled pH are recommended to balance coupling efficiency and stability.
* 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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