To retain antibody bioactivity, mild, near-physiological conditions are often used for conjugation reactions. Under these conditions, endogenous amino acids such as Lys and Cys are chemically reactive and can be used as conjugation sites. One downside in using the endogenous amino acids for ADC development is a heavily dispersed conjugation of DAR caused by the non-uniform distribution of the conjugation sites, especially in the case of Lysine-based conjugations. https://www.creative-biolabs.com/adc/antibody-design-and-conjugation.htm