Boc-PEG2-ethoxyethane-PEG2-benzyl is a heterobifunctional linker comprising a Boc-protected carboxylate at one terminus and a benzyl-protected hydroxyl at the other, bridged by an extended PEG and alkyl ether chain. The Boc group serves as an acid-labile protecting group for the carboxylic acid, enabling selective deprotection to reveal a free carboxylate for amide coupling with amine-containing warheads or E3 ligase ligands. The benzyl group protects the terminal hydroxyl and can be removed under hydrogenolysis conditions to provide a free alcohol for further derivatization. The extended chain length provides substantial conformational flexibility and enhanced aqueous solubility, both of which are important for bridging the spatial gap between the target protein-binding ligand and the E3 ubiquitin ligase-recruiting moiety in PROTAC constructs where greater inter-ligand distances are required for productive ternary complex formation. The mixed PEG and alkyl ether backbone offers a tunable balance of hydrophilicity and lipophilicity, which can be strategically adjusted to optimize cell permeability and solubility. Researchers employ this linker to investigate how extended, flexible linker architectures influence degradation potency, selectivity, and the physicochemical behavior of PROTAC molecules.
Structure of 2111836-22-5
* For research and manufacturing use only. Not for human or clinical use.
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This Boc-PEG2-ethoxyethane-PEG2-benzyl linker is designed to serve as a flexible, solubilizing spacer within PROTAC architectures, helping to tune linker length, conformational freedom, and overall physicochemical behavior of the final conjugate. Its PEG-rich character supports aqueous compatibility and can reduce steric constraints between the target-binding ligand and the E3-recruiting moiety. The benzyl-protected end group and Boc functionality provide practical handles for controlled functionalization, enabling reliable assembly of targeted protein degraders;
Structure: The linker is a PEG-based, ether-rich scaffold incorporating ethoxyethane segments and a benzyl-protected terminus. It contains carbamate functionality from a Boc group and multiple ether linkages that confer flexibility, polarity, and hydrogen-bonding capacity. The benzyl group provides a stable protecting group for downstream coupling.
Reactivity: Boc-protected carbamates are typically deprotected under mild acid conditions to generate a free amine for subsequent PROTAC conjugation. The benzyl protecting group can be removed by hydrogenolysis or other established benzyl-cleavage approaches compatible with common peptide/ligand chemistries. Linker installation generally proceeds via amide or carbamate-forming coupling using standard coupling reagents and polar aprotic solvents, following conventional PROTAC linker functionalization strategies.
* 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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