Fig. 4. Diagram of IgG antibody structure, highlighting the highly conserved glycosylation site at asparagine (Asp) 297 and examples of conjugation sites for the design of antibody drug conjugates (ADCs). IgG antibodies are composed of two light chains (L) and two heavy chains (H), each with a variable domain (V) for antigen binding and one (L) or three (H) constant domains (C). The antigen-binding fragment (Fab) is linked to the crystallisable fragment (Fc) via a hinge region, where the two heavy chains are linked together by two disulfide bonds (blue lines). For ADC conjugation, disulfide bonds, such as those in the hinge region, can be reduced to allow attachment of a cytotoxic drug. Another conventional method is to use for instance a reactive ester modified form of the drug to conjugate it to random lysine (Lys) residues, which are present in every domain. Servier Medical Art PowerPoint image bank was used to construct this diagram.