DBCO-PEG8-NHS ester
DBCO-PEG8-NHS ester is a heterobifunctional PEG linker that combines a strained cyclooctyne (DBCO) click handle with an N-hydroxysuccinimide (NHS) ester for efficient amide coupling. Structurally, it consists of a DBCO moiety connected through an extended polyethylene glycol chain of intermediate length to an activated NHS group, enabling two orthogonal conjugation chemistries. In PROTAC and targeted degradation workflows, the NHS ester can be used to covalently attach the linker to primary amines on lysine residues of proteins or amine-functionalized targeting ligands, while the DBCO group enables strain-promoted azide–alkyne cycloaddition with azide-bearing partners under copper-free conditions. This dual-reactivity supports modular assembly of degradation constructs, such as linking an E3-ligase ligand or targeting moiety to an azide-functional payload or scaffold, improving reaction selectivity and minimizing side reactions. The product is therefore valuable for constructing well-defined, multicomponent PROTAC-like systems for mechanistic studies and optimization of ternary complex formation.
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* For research and manufacturing use only. Not for human or clinical use.
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DBCO-PEG8-NHS ester is a heterobifunctional PROTAC linker designed to connect an NHS-activated amine-reactive handle to a strained cyclooctyne (DBCO) for efficient bioorthogonal conjugation. Its PEG-based spacer improves solubility and provides conformational flexibility, supporting productive ternary complex formation in targeted protein degradation workflows. The molecule is widely used to assemble PROTACs and related degrader constructs via orthogonal coupling strategies, and the detailed structural and reactivity considerations are provided below.
Structure: The linker combines a DBCO moiety with a PEG spacer terminating in an NHS ester. It contains an activated carboxylate for amide formation and a strained alkyne suited for cycloaddition. The PEG chain confers hydrophilicity and flexibility, while the ester is designed for controlled nucleophilic acyl substitution.
Reactivity: The NHS ester reacts with primary amines under mild aqueous conditions to form stable amide bonds, typically using buffered media that maintain amine nucleophilicity while limiting hydrolysis. The DBCO group undergoes strain-promoted azide–alkyne cycloaddition with azide-functional partners without added catalysts. For PROTAC assembly, sequential coupling is commonly used to preserve orthogonality, with purification steps to remove hydrolyzed ester and unreacted reagents.
* 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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