Bis-MAL-Lysine-dPEG®₄-acid

Bis-MAL-Lysine-dPEG®4-acid, product number QBD-10630, is a unique crosslinker from Vector Laboratories, Inc. The two amines of lysine are functionalized with maleimidopropyl groups that react with sulfhydryl groups. The carboxylic acid tail of lysine is conjugated to a single molecular weight, discrete polyethylene glycol (dPEG®) spacer containing a carboxylic acid terminus that can be reacted with free amines or used to provide negative surface charge. The distance from the carbonyl carbon of the dPEG® spacer to the reactive site of the α-amine-conjugated maleimide group is 25 atoms (17.5 Å) long. The distance from the carbonyl carbon of the dPEG® spacer to the reactive site of the ε-amine-conjugated maleimide group is 29 atoms (27.9 Å) long.

By design, the two maleimide groups of Bis-MAL-Lysine-dPEG®4-acid can be used to bridge disulfides. For example, this capability may be useful in antibodies following reduction of the disulfide groups. Moreover, the two maleimide groups can be used to dimerize small molecules or peptides, each of which possesses a single free thiol group. At pH 6.5 – 7.5, maleimide groups react chemoselectively with sulfhydryls. However, above pH 7.5, chemoselectivity is lost, as maleimide groups also will react with free amines.

The carboxylic acid end of the molecule couples with free amines using EDC chemistry to form stable amide bonds. However, if the acid terminus of the molecule is left unreacted, the acid can act as a charge modifier for the molecule to which it is conjugated. Construction of antibody-drug conjugates (ADCs); immobilization of antibodies and antibody fragments; and dimerization of sulfhydryl-containing peptides are some of the possible uses for this product.