Mal-amido-PEG9-NHS ester
CAS No.: 2575631-92-2
Cat No.: BP-501494
4.5 
Mal-amido-PEG9-NHS ester is a heterobifunctional polyethylene glycol (PEG) linker designed for PROTAC and related targeted protein degradation constructs. Structurally, it comprises a maleimide-functionalized end for thiol-reactive conjugation and a terminal N-hydroxysuccinimide (NHS) ester for acylation of primary amines, connected through an extended PEG chain that provides aqueous solubility, reduced nonspecific interactions, and defined spatial separation. In PROTAC assembly, the maleimide group enables site-selective coupling to cysteine-containing ligands or engineered protein-binding modules via thioether formation, while the NHS ester can react with lysine residues or amine-functional handles on the complementary component, allowing controlled “two-step” or orthogonal conjugation strategies. This linker is valuable for building modular degraders, optimizing linker length and flexibility to balance ternary complex formation and degradation potency, and improving experimental reproducibility in conjugation workflows.
Structure of 2575631-92-2
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Mal-amido-PEG9-NHS ester is a polyethylene glycol–based PROTAC linker designed to connect ligands through an NHS-activated ester handle. Its PEG spacer improves solubility and provides conformational flexibility, which can enhance productive ternary complex formation in targeted protein degradation workflows. The amide-linked architecture supports stable conjugate formation, and the NHS ester enables efficient coupling to primary amines on targeting ligands. Detailed structural and reactivity considerations are provided below.
Structure: The linker contains a PEG chain terminating in an NHS ester, along with an amide linkage that anchors the spacer to the mal-amido motif. It features ester and amide carbonyls, ether-rich PEG segments, and an NHS leaving group that supports nucleophilic acyl substitution. Overall, it is designed for aqueous compatibility and flexible presentation of attached ligands.
Reactivity: The NHS ester reacts with primary amines to form stable amide bonds via nucleophilic acyl substitution. Typical conjugations are performed under mildly basic conditions to promote amine nucleophilicity while limiting hydrolysis of the activated ester. Common solvents include aqueous buffer systems with controlled organic cosolvent when needed. No special catalysts are required; careful control of pH, temperature, and reaction time helps balance coupling efficiency against competing 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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