Stable Conjugation with Thiols

Published on 09.12.2014

Maleimide (MAL) reacts rather specific with free thiol groups and forms appropriate conjugates. However, this reaction is slightly reversible, resulting in loss of the conjugation partner.

Amino functions open the maleimido ring structure through hydrolysis with nucleophilc neighboring effect and thus inhibit the undesired release reaction.

Maleimide (MAL) reacts rather specific with free thiol groups and forms appropriate conjugates. However, this reaction is reversible, resulting in loss of the conjugation partner.
Amino functions open the maleimido ring structure through hydrolysis with nucleophilc neighboring effect and thus inhibit the undesired release reaction.

Therefore, our MAL-Dap(Boc) building blocks are ideal tools for persistent conjugation with thiol groups: After removal of the Boc protecting group and conjugation with the mercaptane function, the free methylamino side chain will open the maleimide ring under aqueous conditions. While the conjugation reaction between thiol and cyclic maleimide is reversible, it turns completely stable in the open ring structure. This becomes particularly important in the formation of conjugates with high value components, like in antibody-drug conjugation (ADC).

We supply the appropriate MAL building blocks above promptly from stock and any other MAL conjugate on custom synthesis basis.

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of the Mal-Dap and your compound of choice.

Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates; R.P. Lyon, J.R. Setter, T.D. Bovee, S.O. Doronia, J.H. Hunter, M.E. Anderson, C.L. Balasubramanian, S.M. Duniho, C.I. Leiske, F. Li, P.D. Senter; Nature Biotechnology 2014; 32(10): 1059-1062. DOI:10.1038/nbt.2968.