MAL-Tri-EG-Osu
CAS No.: 2055353-77-8
Cat No.: BP-500758
4.5 
MAL-Tri-EG-Osu is a heterobifunctional PROTAC linker designed to connect a maleimide-functional targeting handle with an O-succinylated triethylene glycol (tri-EG) spacer bearing an activated ester (Osu). Structurally, it contains a maleimide Michael-acceptor for selective conjugation to thiol-containing ligands (e.g., cysteine- or engineered cysteine-bearing binding moieties) and a tri-EG hydrophilic segment that provides conformational flexibility and improved aqueous compatibility while separating the two functional regions. The Osu-activated ester enables efficient amide-bond formation with primary amines, allowing researchers to couple the linker to complementary warheads or affinity groups. In PROTAC design, this architecture supports modular assembly of degraders by enabling sequential, orthogonal bioconjugation steps, facilitating controlled spatial presentation of the recruiter and target-binding components. This product is valuable for systematic linker optimization, helping tune effective ternary complex formation and degradation potency through adjustable length and hydrophilicity, while maintaining robust synthetic accessibility for experimental workflows.
Structure of 2055353-77-8
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MAL-Tri-EG-Osu, is designed to connect a ligand-bearing functional handle to a second binding moiety, enabling formation of ternary, proximity-driven targeted protein degraders. Its features support modular synthesis and reliable conjugation workflows commonly used in PROTAC construction. The linker’s reactivity profile is intended to facilitate efficient coupling while preserving the binding and cooperativity requirements that govern degradation performance. Detailed structural and reactivity considerations are provided below.
Structure: MAL-Tri-EG-Osu comprises a maleimide-derived electrophilic core linked to an oligo-ethylene glycol motif, providing a flexible, hydrophilic spacer. It contains an activated sulfonyl-ester functionality and multiple ether linkages, supporting controlled geometry and compatibility with aqueous-biased PROTAC assembly conditions.
Reactivity: The Osu-type activated ester is suited for nucleophilic acyl substitution with primary amines, forming stable amide linkages under mild base-promoted conditions. Coupling is typically performed in polar aprotic or mixed aqueous solvent systems, using standard PROTAC synthesis practices that minimize hydrolysis. Mechanistically, nucleophilic attack on the activated carbonyl yields the conjugated product, with the leaving group departing to drive completion; catalysts are generally unnecessary beyond controlled pH.
* 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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