DOTA-PEG5-C4-DBCO
DOTA-PEG5-C4-DBCO is a bifunctional PROTAC linker built around a DOTA macrocyclic chelator conjugated to a polyethylene glycol (PEG) spacer and a strained cyclooctyne (DBCO) handle, connected through a C4 linker segment. Structurally, it combines a hydrophilic PEG chain to improve aqueous solubility and reduce nonspecific interactions with a DOTA motif that can coordinate metal ions, while the DBCO group enables rapid copper-free strain-promoted azide–alkyne cycloaddition (SPAAC) for orthogonal bioconjugation. In targeted protein degradation workflows, this linker is useful for modular assembly of degraders or imaging/analytical probes by mediating stable covalent coupling between azide-bearing ligands (e.g., warheads or targeting moieties) and DBCO-functionalized partners. Its PEG and defined linker length support effective spatial presentation of functional groups, which can be critical for maintaining binding and degradation potency. Researchers value it for constructing well-defined, water-compatible conjugates for mechanistic studies and for integrating metal-chelation or click-based labeling into PROTAC design.
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* For research and manufacturing use only. Not for human or clinical use.
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DOTA-PEG5-C4-DBCO is a bifunctional PROTAC linker designed to integrate a macrocyclic chelator motif with a PEG-based hydrophilic spacer and a strained cyclooctyne handle for rapid bioorthogonal conjugation. Its combination of flexible spacing and high reactivity toward azides enables efficient assembly of targeted degradation constructs while supporting aqueous solubility and robust linker performance in conjugation workflows. The following points describe its structure and practical reactivity considerations in detail below.
Structure: The linker contains a DOTA macrocyclic chelator connected through a PEG spacer to a cyclooctyne (DBCO) moiety and an additional carbon linker segment. It features ether-rich PEG connectivity, stable amide/ether functionalities, and a strained alkyne suitable for strain-promoted cycloaddition, supporting water compatibility.
Reactivity: DBCO enables strain-promoted azide–alkyne cycloaddition with azide-bearing partners under catalyst-free, mild aqueous or mixed-solvent conditions. For PROTAC assembly, azide-functional ligands or intermediate conjugates can be reacted with DBCO-containing linker components to form a stable triazole linkage. Typical approaches use buffered, oxygen-tolerant media to preserve sensitive ligands, avoiding strong nucleophiles or conditions that degrade chelator or linker functionalities.
* 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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