DBCO-PEG4-Desthiobiotin
DBCO-PEG4-Desthiobiotin is a bifunctional PROTAC-relevant linker that combines a dibenzocyclooctyne (DBCO) click handle with a terminal desthiobiotin recognition motif connected through a short, flexible polyethylene glycol (PEG) spacer. The PEG4 segment provides conformational mobility and reduces steric interference, while the desthiobiotin moiety enables reversible, high-affinity binding to streptavidin or avidin-family proteins, facilitating controlled recruitment of biotin-tagged components. In targeted protein degradation workflows, this linker can be used to conjugate or position PROTAC constructs, antibody fragments, or other targeting ligands onto streptavidin/avidin scaffolds, thereby improving effective local concentration and orientation for ternary complex formation. Its orthogonal DBCO chemistry supports efficient bioorthogonal conjugation to azide-bearing partners under mild conditions, making it valuable for assembling modular degradation reagents, optimizing linker length, and enabling systematic structure–function studies in targeted protein degradation research.
Structure of 2032788-37-5
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* For research and manufacturing use only. Not for human or clinical use.
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This DBCO-PEG4-desthiobiotin linker is designed for modular PROTAC construction by combining a strain-promoted azide–alkyne cycloaddition (SPAAC) handle with a desthiobiotin recognition element. Its PEG-based spacer improves solubility and spatial presentation, supporting efficient conjugation and controlled ternary-complex formation in targeted protein degradation workflows. The detailed structural and reactivity considerations for using this linker in PROTAC synthesis are provided below.
Structure: The molecule contains a DBCO cyclooctyne moiety connected through a polyethylene glycol spacer to a desthiobiotin-derived scaffold. It features an ether-rich PEG segment for conformational flexibility, along with amide and heterocyclic functional groups typical of biotin analogs. The overall architecture supports water-compatible conjugation and stable linker presentation.
Reactivity: The DBCO group undergoes SPAAC with azide-bearing partners under mild, catalyst-free conditions, typically in aqueous or mixed aqueous/organic solvents compatible with biomolecules. This reaction proceeds via strain-release to form a stable triazole linkage, enabling efficient attachment of the linker to azide-functional PROTAC components. For best performance, azide reagents should be freshly prepared or well-characterized, and reaction conditions should maintain solubility of both conjugates.
* 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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