NH-bis(PEG2-propargyl)

NH-bis(PEG2-propargyl) is a PEG-based, bifunctional linker designed for modular PROTAC assembly, enabling efficient conjugation between a ligand and an E3-recruiting moiety. Its flexible ethylene glycol segments support productive linker conformations, while the terminal propargyl groups provide reliable handles for orthogonal coupling chemistries. This product is well suited for researchers optimizing targeted protein degradation constructs; the following sections describe its structure and practical reactivity considerations in detail.

Structure: NH-bis(PEG2-propargyl) is a bifunctional polyethylene glycol linker containing an amide-linked nitrogen core and two short PEG arms terminated with propargyl alkynes. It features ether linkages that impart flexibility, along with C≡C carbon–carbon triple bonds for click-type reactivity and an amide linkage that can influence polarity and solubility.

Reactivity: The terminal propargyl groups are compatible with copper-catalyzed azide–alkyne cycloaddition or related alkyne–azide coupling strategies commonly used in PROTAC synthesis. Typical approaches employ Cu(I) generation from copper salts with stabilizing ligands, in polar aprotic or mixed aqueous/organic solvents, under conditions that preserve sensitive ligands. Reaction success depends on maintaining appropriate alkyne accessibility and minimizing alkyne oxidation or side reactions.