Boc-HyNic-PEG2-DBCO
Boc-HyNic-PEG2-DBCO is a bifunctional PROTAC linker built on a short, two–ethylene glycol (PEG2) spacer that connects a Boc-protected hyNic (hydrazinonicotinamide) handle to a strained cyclooctyne (DBCO) for copper-free click chemistry. The hyNic group is designed to be compatible with hydrazone-based conjugation strategies, enabling attachment to aldehyde-bearing targeting ligands (or other biomolecules) through reversible hydrazone formation under typical experimental conditions, while the Boc protecting group improves handling stability prior to conjugation. The DBCO moiety then provides high-efficiency, bioorthogonal ligation to azide-functional partners via strain-promoted azide–alkyne cycloaddition, allowing modular assembly of multi-component degradation constructs. In targeted protein degradation research, this linker is valuable for preparing PROTAC-relevant conjugates that require orthogonal coupling steps, improved aqueous solubility, and controlled spatial separation between binding and recruitment elements, thereby facilitating systematic structure–activity optimization.
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* For research and manufacturing use only. Not for human or clinical use.
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Boc-HyNic-PEG2-DBCO is a multifunctional PROTAC linker designed to integrate a hydrazine-reactive HyNic handle with a PEG spacer and a DBCO cyclooctyne for bioorthogonal conjugation. Its features support modular assembly of targeted degradation constructs, enabling efficient coupling of ligands and subsequent attachment to biomolecular targeting partners under mild conditions. The structure and reactivity characteristics are described in detail below.
Structure: The molecule combines a Boc-protected HyNic hydrazine motif with a short polyethylene glycol spacer and a DBCO cyclooctyne. It contains carbamate and ether linkages, along with an alkyne-rich strained ring system that supports rapid click-type reactivity. The PEG segment increases aqueous compatibility and conformational flexibility.
Reactivity: PROTAC construction typically uses HyNic for hydrazone formation with aldehyde-functional targeting ligands, followed by DBCO-mediated strain-promoted azide–alkyne cycloaddition. Boc protection enables controlled reactivity during stepwise synthesis and conjugation workflows. Common approaches employ mild aqueous or mixed solvent conditions, with careful pH control for hydrazone exchange, and no copper catalyst for the DBCO click step, reducing metal-associated 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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