Products

Permanent Linkers with Maleimide Function

Michael addition of a thiol to a maleimide is commonly used for numerous bioconjugations. Several

commercial constructs like Brentuximab vedotin, Trastuzumab emtansine, and Cimzia contain a thiol-

maleimide adduct. However, this reaction is reversible. During the journey of an appropriate thioether

containing drug through physiological media, this bond can break, and fragments are released which might

contribute to certain unwanted or even toxic reactions.

Fig. 1: Maleimides bind reversibly to thiols resulting in thioethers. This linkage turns stable once the

maleimide ring is opened through hydrolysis.

However, if the succinimide moiety of a maleimide-thiol conjugate is hydrolyzed, the ring-opened product is

fully stabilized towards cleavage (Fig. 1). The rates of ring-opening hydrolysis are greatly accelerated by

electron withdrawing N-substituents and good nucleophiles in the proximity of the carbonyl functions. Thus,

conjugates made with nucleophilic side chains and electron-withdrawing maleimides may be purposefully

hydrolyzed to their ring-opened counterparts and ensure good in vivo stability.

Mal-Et-OH

Mal-NH2*HCl

DBCO-mal

DBCO-PEG(4)-mal

MeTz-PEG(4)-mal