Boc-PEG4-methyl propionate is a heterobifunctional PEG linker featuring a Boc-protected carboxylate at one terminus and a methyl ester at the other, connected through a tetraethylene glycol spacer. The Boc group provides acid-labile protection for the proximal carboxylic acid, while the methyl ester serves as an acid-labile protecting group for the distal carboxylate. This differentially protected architecture enables sequential deprotection and conjugation strategies: the Boc group can be removed under mild acidic conditions to reveal a free carboxylic acid for initial amide coupling with one ligand, followed by selective hydrolysis of the methyl ester under basic conditions to liberate the second carboxylate for coupling with a different amine-containing ligand. The orthogonal stability of Boc and methyl ester groups under their respective deprotection conditions allows for selective, stepwise functionalization without cross-reactivity. The PEG spacer enhances aqueous solubility and provides conformational flexibility necessary for productive ternary complex assembly. Researchers employ this linker to construct PROTACs with defined, stepwise conjugation protocols, investigating how controlled sequential installation of target protein-binding and E3 ligase-recruiting ligands influences degradation potency, selectivity, and reproducibility in targeted protein degradation research.
Structure of 2100306-74-7
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This oligoether linker bears differently protected carboxyl termini, enabling sequential unveiling and directional PROTAC assembly. The acid-sensitive tert-butyl ester and hydrolytically removable methyl ester provide complementary synthetic entry points across a flexible, polar spacer. Its structure and reaction behavior follow.
Structure: A linear oligoether chain connects tert-butyl and methyl propanoate termini. The molecule contains multiple rotatable ether bonds and ester carbonyls but no free nucleophile. Distinct ester substituents create differentiated ends that can respond differently to acidic and hydrolytic conditions.
Reactivity: Acid treatment preferentially cleaves the tert-butyl ester, whereas controlled saponification can expose the methyl-protected acid. The selected carboxyl group may then be activated with a carbodiimide or uronium reagent for amide coupling to an amine-bearing ligand in a polar aprotic solvent with base. Reaction sequence should reflect the acid or base sensitivity of the ligand components already installed.
* 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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