UCLA researchers in the Department of Chemistry and Biochemistry have proposed a one-step radical mechanism for disulfide bioconjugation that overcomes many concerns associated with the free cysteine residues that result from current bioconjugation techniques.
The post-translational modification of proteins has a number of important biological applications, including the development of novel drugs. Although its reactive thiol group makes cysteine an ideal site for modification, cysteine is typically bonded in a disulfide bridge. The modification of cysteine disulfide bonds is difficult since these bonds play a crucial role in protein structures. Additionally, current modification techniques require a reduction step prior to bioconjugation that leads to the production of free cysteine residues. Cysteine residues cause protein unfolding and aggregation and can compromise protein structure and function.
UCLA researchers in the Department of Chemistry and Biochemistry have proposed a radical mechanism for disulfide bioconjugation. The proposed mechanism allows for peptide modification through selective one-step conjugation of disulfide bonds. Importantly, this mechanism does not require the reduction step of current techniques and allows for rapid disulfide bioconjugation without the production of free cysteine residues. The applications of the proposed mechanism range from antibody drug conjugation to more general protein conjugation.
antibody drug conjugation; bioconjugation; disulfide bioconjugation; post-translational modification; cysteine radical