Mal-PEG16-NHS ester
Cat No.: BP-501945
4.5 
Mal-PEG16-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker featuring a maleimide group for selective thiol conjugation and an N-hydroxysuccinimide (NHS) ester for acylation of primary amines. The linker consists of a long, flexible PEG chain that increases aqueous solubility and spacing between connected biomolecular domains, while maintaining reactivity at both termini. In PROTAC and targeted protein degradation workflows, this type of dual-reactive linker enables modular assembly by first coupling the NHS ester to an amine-bearing ligand (for example, a targeting moiety or E3 ligase binder) and subsequently reacting the maleimide with a cysteine- or thiol-functionalized partner, thereby positioning the two ligands at an optimized distance and orientation to support productive ternary complex formation. Its value lies in providing a robust, experimentally convenient platform for generating linker-defined conjugates, improving conjugation efficiency, and facilitating systematic structure–activity studies of linker length and flexibility in targeted degradation research.
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* For research and manufacturing use only. Not for human or clinical use.
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Mal-PEG16-NHS ester is a PEG-based heterobifunctional linker designed for efficient conjugation in PROTAC workflows, enabling the installation of a maleimide handle for thiol-directed coupling and an NHS-ester handle for amide bond formation with primary amines. Its high aqueous compatibility and flexible PEG spacer support favorable linker presentation to ligands, which can improve conjugation efficiency and the effective geometry of ternary-complex forming PROTAC constructs. Detailed structural and reactivity guidance is provided below.
Structure: The molecule combines a maleimide electrophile with an NHS-activated ester on a long polyethylene glycol chain. It contains an amide-forming NHS carbonate motif and a conjugated maleimide double bond, providing stable linkages and a thiol-reactive alkene. The PEG segment imparts hydrophilicity and conformational flexibility.
Reactivity: The NHS ester reacts with primary amines to form stable amide bonds under mildly basic aqueous or mixed solvent conditions, while the maleimide undergoes Michael-type addition with thiols to yield a thioether linkage. Typical PROTAC assembly uses sequential or orthogonal coupling: first amine-to-NHS conjugation, then thiol-to-maleimide attachment. Mild, thiol-compatible buffers and freshly prepared thiol nucleophiles are commonly used; avoid strong nucleophiles and conditions that promote maleimide 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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