NH-bis(C1-PEG1-Boc) is a branched PEG linker featuring a central primary amine flanked by two Boc-protected carboxylate arms, each connected through short PEG spacers. This compact, symmetric architecture provides a versatile building block for PROTAC assembly, where the primary amine can be selectively acylated with carboxylic acid-containing ligands, such as target protein warheads or E3 ubiquitin ligase-recruiting moieties, via standard amide coupling chemistry. The two Boc-protected carboxylate groups, upon sequential or simultaneous deprotection under mild acidic conditions, yield free carboxylic acids that serve as additional conjugation sites for amine-bearing ligands. The branched topology enables the construction of multivalent or heterobifunctional PROTACs from a single linker node, allowing researchers to modulate the spatial orientation and effective local concentration of each ligand within the ternary complex. The short PEG arms maintain a compact molecular profile while providing sufficient flexibility to accommodate the conformational requirements of productive E3 ligase-target protein engagement. Researchers employ this linker to investigate how branched, compact architectures influence degradation efficiency, selectivity, and the physicochemical properties of resulting PROTAC molecules.
Structure of 2171072-53-8
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This compact branched linker carries a free primary amine and protected carboxyl termini, supporting early amine conjugation followed by acid unveiling. Its symmetric ether-containing arms can create a defined branch point for compact PROTAC or multivalent degrader exploration. Structural and reaction details follow.
Structure: A primary amine is attached to a substituted carbon that connects ether-linked tert-butyl propanoate arms. The molecule contains ester carbonyls, ether bonds, a nucleophilic amino group, and a tetrahedral branch center; its rotatable single bonds confer flexibility around a compact core.
Reactivity: The primary amine can undergo amide formation with an activated carboxylic acid or acyl chloride, or carbamate formation with a chloroformate, using a tertiary base in an anhydrous polar solvent. Acidic cleavage then converts the tert-butyl esters to carboxylic acids for further coupling. Protecting the amine before ester deprotection may simplify selectivity when multiple acylations are planned.
* 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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