t-Boc-Aminooxy-PEG12-NHS ester
t-Boc-Aminooxy-PEG12-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker designed for PROTAC and targeted protein degradation workflows. Structurally, it contains an NHS-activated ester for efficient acylation of nucleophiles (commonly primary amines on ligands or warheads) and an aminooxy handle protected as a tert-butoxycarbonyl (t-Boc) group, enabling subsequent oxime/oxime-ether formation after deprotection. The PEG12 chain provides a flexible, hydrophilic spacer that can reduce steric clashes and modulate the effective distance and orientation between the two binding elements of a PROTAC, thereby improving formation of the ternary complex with the E3 ligase and target protein. In experimental design, this linker supports modular conjugation strategies: first coupling the NHS ester to a ligand bearing an amine, then converting the aminooxy functionality to an oxime linkage for stable attachment to an aldehyde-bearing partner. Its utility lies in enabling controlled, reproducible synthesis of degraders with tunable linker length and physicochemical properties.
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* For research and manufacturing use only. Not for human or clinical use.
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This PROTAC linker reagent enables efficient conjugation between an amine-containing ligand and an NHS-activated partner, supporting the modular assembly of targeted protein degraders. Its PEG-based spacer promotes solubility and conformational flexibility, which can improve productive ternary complex formation while reducing steric constraints at the binding interfaces. The sections below describe the linker’s structure and the practical reactivity considerations for PROTAC construction.
Structure: The linker is a PEG-based chain terminated with an N-hydroxysuccinimide ester, paired with a protected aminooxy functionality. It contains an NHS carbonate/ester linkage, ether-rich repeating units, and a Boc-protected aminooxy group, providing a hydrophilic, flexible scaffold with stable covalent handles for bioconjugation.
Reactivity: The NHS ester reacts with primary amines via nucleophilic acyl substitution to form a stable amide bond under mildly basic aqueous or mixed solvent conditions. For aminooxy coupling, the Boc protection is removed to generate an aminooxy nucleophile, which can participate in oxime or related carbonyl-directed ligations depending on the complementary partner. Standard carbodiimide-free NHS coupling workflows are commonly used, with careful control of pH to maintain NHS reactivity.
* 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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