Propane, 2,2-[1,2-ethanediylbis(oxy)]bis- is a di-ether–containing, flexible aliphatic linker featuring an ethylene glycol–type bis(oxy) motif embedded within a propane backbone. Its structural design provides a suitable spacer that can transmit conformational freedom between a ligand-binding module and an E3-recruiting or target-binding moiety in PROTAC architectures. By presenting ether oxygen atoms along the linker, the compound can support favorable local solvation and hydrogen-bonding interactions that may influence the productive alignment of the two binding partners, thereby improving the likelihood of ternary complex formation. In targeted protein degradation research, such linkers are commonly used to tune distance and relative orientation between functional warheads without introducing reactive groups that would interfere with conjugation chemistries. This makes the material a practical building block for systematic linker-length and geometry optimization in PROTAC studies.
Structure of 3944-35-2
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This PROTAC linker is designed to provide a flexible, ether-rich connection motif that can be used to spatially organize a target-binding ligand and an E3 ligase ligand within a degrader construct. Its structural features support compatibility with common PROTAC assembly strategies, enabling reliable synthesis of bifunctional molecules for targeted protein degradation studies. The detailed structural and synthetic considerations are provided below.
Structure: The linker comprises an alkyl propane backbone bearing an ethylene glycol–derived bis(oxy) motif, featuring multiple ether linkages and an internal di-ether connectivity pattern. Such oxygen-rich segments contribute to polarity, conformational flexibility, and hydrogen-bond acceptor character, which can influence linker solvation and degrader geometry.
Reactivity: For PROTAC construction, this type of linker is typically employed in coupling workflows that form stable carbon–heteroatom or carbon–carbon connections to ligand functional groups. Suitable approaches include nucleophilic substitution or ether/ester-forming reactions depending on the ligand handles, commonly using polar aprotic solvents and base or activating reagents to promote controlled bond formation. Reaction conditions are selected to preserve sensitive ligand functionalities and minimize side reactions such as over-alkylation or ether cleavage.
* 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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