DBCO-NHCO-PEG6-maleimide
DBCO-NHCO-PEG6-maleimide is a heterobifunctional, PEG-based linker designed for copper-free strain-promoted azide–alkyne cycloaddition (SPAAC) and thiol–maleimide conjugation. Structurally, it contains a DBCO (dibenzocyclooctyne) group for rapid reaction with azide-bearing partners, an amide-linked PEG6 spacer that provides aqueous solubility and molecular flexibility, and a terminal maleimide for selective coupling to cysteine or other thiol-containing biomolecules via Michael addition. In PROTAC and targeted protein degradation workflows, this linker enables modular assembly: one degradation module or targeting ligand can be functionalized with an azide to react with DBCO, while the second module can be introduced through a thiol handle to form a stable thioether. Its PEG spacer helps reduce steric hindrance and can improve conjugate homogeneity, making it valuable for constructing well-defined, experimentally tractable PROTACs and related targeted degraders for mechanistic and binding studies.
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* For research and manufacturing use only. Not for human or clinical use.
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This DBCO-NHCO-PEG6-maleimide linker is designed to enable efficient, modular assembly of PROTAC conjugates through orthogonal bioorthogonal chemistries. Its DBCO handle supports rapid strain-promoted azide–alkyne cycloaddition, while the maleimide group enables selective thio-Michael addition to cysteine-containing ligands. The PEG-based spacer improves solubility and reduces steric constraints, facilitating reliable conjugation and subsequent targeted protein degradation workflows. Detailed structural and reactivity considerations are provided below.
Structure: The linker contains a DBCO cyclooctyne moiety, an amide connection, and a PEG-based hydrophilic spacer terminating in a maleimide electrophile. It features conjugated ring strain for cycloaddition and an activated alkene within the maleimide for nucleophilic addition, with multiple ether linkages enhancing aqueous compatibility.
Reactivity: Conjugation typically proceeds via two complementary steps: strain-promoted azide–alkyne cycloaddition using an azide partner under mild, catalyst-free conditions, and thio-Michael addition of the maleimide to thiols (often cysteine-containing biomolecules) to form stable thioether linkages. Experiments are commonly performed in aqueous buffers compatible with maleimide stability, with careful control of pH and thiol availability to minimize hydrolysis or side reactions.
* 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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