HyNic-PEG2-DBCO
HyNic-PEG2-DBCO is a bifunctional PEG-based linker reagent combining a hydrazine (HyNic) handle with a strained cyclooctyne (DBCO) for copper-free click conjugation. Structurally, it provides a short ethylene glycol spacer that separates the reactive termini, improving accessibility of the DBCO group for subsequent azide-bearing partners while maintaining a stable hydrazine-derived attachment point for introducing the linker onto carbonyl-containing targeting or carrier molecules. In PROTAC and targeted degradation workflows, this type of linker is used to modularly connect a protein-binding ligand (or other functional module) to a second component through orthogonal chemistries: the HyNic moiety enables site-selective formation of hydrazone-type conjugates, and the DBCO group enables rapid reaction with azides to generate a stable triazole linkage. Its utility lies in enabling controlled, modular assembly of degradation constructs with minimized cross-reactivity, facilitating systematic optimization of conjugation geometry and, consequently, ternary complex formation and degradation performance.
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* For research and manufacturing use only. Not for human or clinical use.
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HyNic-PEG2-DBCO is a bifunctional, PEG-based PROTAC linker designed to connect a hydrazine-containing warhead handle to a strained-alkyne (DBCO) partner for efficient bioorthogonal conjugation. Its flexible polyethylene glycol spacer supports favorable linker dynamics and can help maintain productive geometry between targeting and E3-ligase moieties. In PROTAC workflows, this linker enables modular assembly and subsequent attachment to azide-bearing components via fast, selective click chemistry; detailed structural and reactivity considerations are provided below.
Structure: The linker combines a hydrazine (HyNic) functional group with a short, flexible PEG spacer and a cyclooctyne-derived DBCO strained-alkyne. It contains ether linkages within the PEG segment and a strained alkyne capable of rapid cycloaddition, yielding a stable triazole linkage after conjugation.
Reactivity: Conjugation typically proceeds through strain-promoted azide–alkyne cycloaddition, which does not require copper catalysts. Suitable conditions generally use aqueous or mixed aqueous buffers compatible with biomolecules, with mild temperatures to preserve protein integrity. The mechanism relies on the high reactivity of the DBCO strained alkyne toward azides, forming a stable triazole adduct; reaction progress is commonly monitored by analytical chromatography or spectroscopy.
* 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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