DBCO-NH-PEG7-C2-NHS ester
DBCO-NH-PEG7-C2-NHS ester is a heterobifunctional PEG-based linker that combines a cyclooctyne (DBCO) for strain-promoted azide–alkyne cycloaddition with an NHS-activated ester for rapid coupling to primary amines on proteins, peptides, or other targeting ligands. Structurally, it features a PEG7 chain providing aqueous solubility and spatial separation, a short ethylene (C2) spacer that tunes linker flexibility, and an amide-forming NHS ester that reacts under mild basic conditions to yield stable amide bonds. In PROTAC and targeted degradation workflows, this linker enables modular assembly: one component can be functionalized with azide handles and conjugated to DBCO-bearing partners via bioorthogonal click chemistry, while the NHS ester facilitates attachment of the linker to amine-containing warheads, E3 ligands, or carrier scaffolds. Its utility lies in improving conjugation efficiency, reducing steric hindrance, and allowing controlled geometry between binding domains to support efficient ternary-complex formation and degradation studies.
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* For research and manufacturing use only. Not for human or clinical use.
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This DBCO-NH-PEG7-C2-NHS ester is a bifunctional PROTAC linker designed to connect an NHS-activated targeting handle to a strained cyclooctyne (DBCO) for efficient bioorthogonal conjugation. Its PEG-based spacer and amide linkage promote solubility and conformational flexibility, helping maintain productive proximity between the ligand and the recruited E3 ligase module. The molecule will be described in detail below, including its structure and practical reactivity considerations for PROTAC construction.
Structure: The linker contains a DBCO cyclooctyne moiety for strain-promoted azide-alkyne cycloaddition, an amide-linked PEG spacer, and a terminal NHS ester for acyl transfer. It features ether-rich PEG segments that enhance hydrophilicity and flexible spacing, with stable covalent bonds connecting the functional groups.
Reactivity: The NHS ester reacts with primary amines under mildly basic aqueous buffer conditions to form stable amide bonds, enabling installation of the targeting ligand. The DBCO group undergoes strain-promoted azide–alkyne cycloaddition with azide-functional partners without added catalysts. For PROTAC assembly, sequence the amine coupling first, then perform the bioorthogonal conjugation in compatible solvent systems that preserve NHS reactivity during the initial step and maintain DBCO cycloaddition efficiency thereafter.
* 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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