Azido-PEG3-S-PEG4-propargyl
CAS No.: 2055041-24-0
Cat No.: BP-501631
Purity: 98%
4.5 
Azido-PEG3-S-PEG4-propargyl is a heterobifunctional polyethylene glycol (PEG) linker featuring an azide group and a terminal propargyl alkyne, connected through a thioether (S) segment and PEG3/PEG4 spacer arms. The PEG backbone provides water solubility and conformational flexibility, while the thioether linkage maintains a defined connectivity between the two PEG regions. In PROTAC and targeted protein degradation workflows, this linker is designed to enable modular conjugation to two different molecular components using orthogonal bioorthogonal chemistries: the azide can undergo CuAAC with terminal alkynes or SPAAC with strained cyclooctynes such as DBCO or BCN, while the propargyl group can undergo CuAAC with azide-bearing partners. Its balanced spacer length and flexible ether environment help minimize steric interference, supporting productive formation of the ternary complex between a target-binding ligand and an E3 ligase recruiter. This makes it a practical tool for constructing degraders and for optimizing linker placement to improve degradation efficiency and experimental tractability.
Structure of 2055041-24-0
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Azido-PEG3-S-PEG4-propargyl is a heterobifunctional PEG-based linker designed to enable modular assembly of PROTAC molecules through orthogonal “click” chemistries. Its flexible poly(ethylene glycol) segments help tune effective linker length and solvation, while the azide and propargyl termini provide reliable handles for sequential conjugation to ligands. The combination of sulfur-containing connectivity and reactive end groups makes it well suited for constructing targeted protein degraders, as detailed below.
Structure: The linker contains flexible PEG chains connected through a sulfur-containing linkage, providing conformational mobility and improved aqueous compatibility. It bears an azide functional group and a terminal propargyl (alkyne) group, enabling bioorthogonal coupling. The molecule features ether linkages typical of PEG and stable covalent C–N and C–C frameworks.
Reactivity: PROTAC assembly can be performed via copper(I)-catalyzed azide–alkyne cycloaddition between the azide and an appropriate alkyne-bearing partner, or via strain-promoted azide–alkyne cycloaddition when using a cyclooctyne/strained alkyne handle. Typical conditions use copper(I) generated in situ, with inert atmosphere and aqueous/organic co-solvents to maintain solubility. The reaction proceeds through formation of a metallated acetylide and subsequent cycloaddition to yield a stable triazole linkage.
* 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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