The maleimide-thiol chemistry is widely used to synthesize bioconjugates, including conjugate vaccines and antibody drug conjugates (ADC) . The resultant thiosuccinimide linker in these bioconjugates, (Figure , structure III) is unstable in vivo due to the retro-Michael reaction . Molecules with free thiols that are available in appreciable concentrations in vivo, react with the thiosuccinimide linker, releasing the antigen or the drug that is linked to the carrier protein. This process known as thiol exchange could have a negative impact for the biological activity and cytotoxicity for the synthesized bioconjugate .