Folate-PEG3-NHS ester
Folate-PEG3-NHS ester is a heterobifunctional PROTAC linker that couples a folate-targeting ligand to a short polyethylene glycol spacer terminating in an N-hydroxysuccinimide (NHS) ester. Structurally, it features a folate moiety connected through a three-unit PEG chain, with the NHS group providing a reactive acylating handle for forming stable amide bonds with primary amines on an E3 ligase ligand or other targeting module. In targeted protein degradation workflows, this linker enables modular assembly by spatially separating the folate-binding domain from the conjugation site, which can improve presentation and accessibility of the binding interface while maintaining efficient coupling chemistry. Its value lies in facilitating rapid, reproducible synthesis of folate-directed degraders or conjugates, supporting experiments that probe receptor-mediated uptake, ternary-complex formation, and degradation efficiency across different E3 ligase formats.
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* For research and manufacturing use only. Not for human or clinical use.
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Folate-PEG3-NHS ester is a PEG-based, folate-functional linker designed for efficient conjugation of targeting ligands in PROTAC and related targeted protein degradation workflows. Its NHS-ester handle enables rapid coupling to primary amines under mild conditions, facilitating the assembly of bifunctional degraders with improved aqueous compatibility and reduced steric constraints. The points below describe its structure and practical reactivity for experimental construction of PROTAC architectures.
Structure: The molecule contains a folate targeting moiety connected through a short polyethylene glycol chain, terminating in an N-hydroxysuccinimide (NHS) ester. It features an amide-forming activated carboxylate, ether linkages within the PEG segment, and aromatic heterocycles typical of folate derivatives. Overall, it is designed for aqueous solubility and flexible linker conformations.
Reactivity: The NHS ester reacts with primary amines to form stable amide bonds via nucleophilic acyl substitution, releasing NHS as a leaving group. Suitable conditions generally use mildly basic aqueous buffers that preserve NHS ester reactivity while maintaining amine nucleophilicity. Common coupling approaches rely on room-temperature incubation and careful pH control; no special catalysts are typically required. After coupling, excess activated linker is removed by standard purification methods to obtain the amine-conjugated intermediate for subsequent 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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