cysteine drug

Cysteine residues serve essential roles in protein structure and function due to their highly reactive thiol side chains that form inter or intra molecular di-sulfide bonds to enable correct protein folding. Thiol reactivity also provides an appealing route for conjugating toxic agents to antibodies. A full IgG scaffold contains 16 cysteine pairs, forming 12 intra- and 4 inter-chain disulfide bonds. Due to higher solvent accessibility, the four inter-chain disulfides forming Cys residues are the main targets for conjugation, but occasions where conjugation occurred on intra-chain cysteines have also been reported. What’s more, strategies using engineered Cys residues for site specific conjugation without the partial reduction of the endogenous disulfide bonds have been well-established and termed EnCys-mAb. https://www.creative-biolabs.com/adc/cysteine-based-conjugation.htm