Fmoc-NMe-PEG4-NHS ester
Fmoc-NMe-PEG4-NHS ester is an amine-reactive polyethylene glycol (PEG) linker bearing an N-hydroxysuccinimide (NHS) ester for efficient formation of stable amide bonds with primary amines. Structurally, it combines an Fmoc-protected secondary amine functionality with a short, flexible PEG chain length that provides aqueous solubility, reduced nonspecific protein adsorption, and improved linker mobility. In PROTAC and targeted protein degradation constructs, this type of linker is used to conjugate the “handle” on one module (for example, an amine-containing ligand or intermediate) to the complementary partner while maintaining an appropriate spatial separation to support ternary complex formation. The PEG spacer and NHS chemistry facilitate reproducible coupling under mild conditions, enabling modular synthesis and systematic optimization of linker length and flexibility. As a result, it is valuable for researchers developing degraders that require robust, water-compatible bioconjugation and tunable geometry between recognition and recruitment domains.
Structure of 2228857-30-3
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* For research and manufacturing use only. Not for human or clinical use.
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Fmoc-NMe-PEG4-NHS ester is a PEG-based activated linker designed for efficient conjugation in PROTAC assembly workflows. Its combination of an NHS ester handle with an Fmoc-protected amine functionality enables modular synthesis and purification-friendly intermediates, supporting reliable attachment of ligands to targeting and recruiting modules. The flexible polyethylene glycol segment can help tune solubility and reduce steric constraints during ternary complex formation. Detailed structural and reactivity considerations are provided below.
Structure: The molecule contains an Fmoc-protected nitrogen, a PEG oligomeric spacer, and an N-hydroxysuccinimide ester. It features stable aromatic carbamate and ether linkages within a flexible polyether chain, providing a polar, water-compatible scaffold with an electrophilic acyl group for amide formation.
Reactivity: The NHS ester is reactive toward primary amines under mild, aqueous-compatible conditions, typically forming amide bonds via nucleophilic acyl substitution. Suitable bases such as tertiary amines are commonly used to promote coupling while maintaining NHS reactivity. Reactions are generally performed in buffered or mixed aqueous/organic solvents at controlled pH, avoiding prolonged exposure to strong nucleophiles that could hydrolyze the activated ester.
* 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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