m-PEG24-NHS ester
m-PEG24-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker featuring a methoxy-terminated PEG chain and an N-hydroxysuccinimide (NHS) ester for amide-bond formation that provides aqueous solubility, spacing, and reduced nonspecific protein interactions. In PROTAC and targeted protein degradation constructs, the NHS ester enables efficient conjugation to primary amines on ligands (e.g., lysine residues or amine-functionalized warheads) under standard coupling conditions, yielding a stable amide linkage while the PEG segment acts as a molecular “molecular ruler” to tune the relative orientation and effective distance between the two binding modules. This linker is therefore valuable for optimizing ternary complex formation and improving solubility and handling of conjugates, particularly when steric constraints or unfavorable proximity between targeting and E3-recruiting components limit degradation efficiency.
Structure of 2395839-96-8
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m-PEG24-NHS ester is a polyethylene glycol (PEG) based linker designed for efficient conjugation in PROTAC workflows, enabling the attachment of targeting ligands to protein-binding modules through stable amide formation. Its PEG scaffold improves solubility and provides a flexible spacer that can help tune effective distances and reduce steric constraints during ternary-complex formation. The following sections describe the linker’s structure and the practical reactivity considerations for constructing PROTACs in detail below.
Structure: The linker consists of a methoxy-terminated PEG chain bearing an N-hydroxysuccinimide (NHS) ester at the opposite terminus. It contains an NHS-activated carbonyl for acyl transfer and ether linkages within the PEG backbone, yielding a hydrophilic, flexible spacer suitable for bioconjugation.
Reactivity: NHS esters react with primary amines to form stable amide bonds, typically under mildly basic conditions that preserve NHS activity while promoting nucleophilic acyl substitution. Commonly used solvents include aqueous buffers with compatible organic cosolvents, and reactions are performed at temperatures that maintain NHS integrity. No special catalysts are required; careful pH control and timely quenching help minimize hydrolysis and maximize coupling efficiency during PROTAC assembly.
* 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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