4-Maleimidobutyric acid

Description

4-(2,5-dioxo-2H-pyrrol-1(5H)-yl)butanoic acid contains a maleimide group and a terminal carboxylic acid. The terminal carboxylic acid can react with primary amine groups in the presence of activators (e.g. EDC, or HATU) to form a stable amide bond. The maleimide group will react with a thiol group to form a covalent bond, enabling the connection of biomolecule with a thiol.

Chemical Properties

White Solid

Uses

1. A short crosslinking reagent
2. Modification reagent for thiol groups in proteins
3. Maleimide Derivatives
4. MTS & Sulfhydryl Active Reagents

Uses

4-Maleimidobutyric Acid is a short crosslinking reagent.

Synthesis

General procedure for the synthesis of 4-maleimidobutyric acid from the compound (CAS: 15938-22-4): compound (II) (191 g, 0.95 mol, X = 3) and 600 mL of acetonitrile were added to a 1000 mL three-necked flask, followed by the addition of diisopropylethylamine (363 g, 2.8 mol) and a solution of phenyl 4-nitro trifluoroacetate. Phenyl 4-nitrilotrifluoroacetate (353.4 g, 1.5 mol) dissolved in 300 mL of acetonitrile was added dropwise to the reaction system and the reaction temperature was controlled to be between -5 and 10 °C. After completion of the reaction, the mixture was dried, 400 mL of water was added and the pH was adjusted to 3-4 with concentrated hydrochloric acid. 4-nitrophenol was removed by filtration and the filtrate was extracted three times with dichloromethane, the organic phases were combined, washed with water and dried with anhydrous magnesium sulfate. After concentration and drying, 129 g of light yellow solid was obtained. 111 g of white solid was obtained by recrystallization from mixed solvent of ethyl acetate and petroleum ether, 99 g was weighed after drying, and the purity was 98.4% by HPLC, and the yield was 57.0%.

IC 50

Alkyl-Chain

References

[1] Patent: CN105037237, 2017, B. Location in patent: Paragraph 0063-0066
[2] Organic and Biomolecular Chemistry, 2009, vol. 7, # 17, p. 3400 - 3406