m-PEG49-NHS ester
m-PEG49-NHS ester is a monofunctional methoxy-PEG linker bearing a terminal N-hydroxysuccinimide (NHS) ester, designed for stable conjugation chemistry in targeted protein degradation workflows. Structurally, it consists of a long, flexible polyethylene glycol chain that provides hydrophilicity and conformational spacing, terminating in an NHS-activated carboxylate surrogate that readily reacts with primary amines on ligands such as lysine-bearing peptides, engineered protein-binding motifs, or amine-functionalized small molecules. In PROTAC design, this linker serves as a spacer that can reduce steric clashes between the E3 ligase recruiter and the target-binding warhead while positioning them to favor productive ternary complex formation. Its PEG architecture often improves solubility and can help maintain functional presentation of both binding elements during synthesis and assay development, making it a practical tool for constructing and optimizing degraders that require controlled amide bond formation under standard coupling conditions.
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m-PEG49-NHS ester is a polyethylene glycol (PEG)-based N-hydroxysuccinimide (NHS) ester linker designed for efficient conjugation in PROTAC workflows. Its PEG spacer improves solubility and can reduce non-specific interactions, while the NHS ester enables rapid, chemoselective coupling to primary amines on ligands. This combination supports modular assembly of targeted protein degraders, and the subsequent points describe the structure and practical reactivity considerations in detail below.
Structure: The linker comprises a PEG chain terminating in an NHS ester, featuring an activated carbonate-like acyl group attached to the NHS moiety. It contains ether linkages along the PEG backbone and an electrophilic carbonyl suitable for acyl substitution. Overall, it is typically water-compatible and flexible.
Reactivity: NHS esters react with primary amines via nucleophilic acyl substitution, forming stable amide bonds while releasing NHS. For PROTAC construction, coupling is commonly performed under mildly basic conditions to promote amine nucleophilicity while preserving NHS ester integrity. Typical solvents include aqueous buffers or mixed aqueous/organic systems, and reactions are often run at controlled temperature with careful exclusion of competing amines and water to limit hydrolysis.
* 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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