Engineered antibodies and antibody fragments have emerged as versatile vehicles for antibody–drug conjugates. The conjugation strategy plays an important role in determining the conjugate’s in vitro and in vivo behavior. For site-specific payload conjugation, we generated mutant antibody variants of antibodies. The model antibody was recombinantly expressed and purified by protein A chromatography. We confirmed that mutant antibodies retained comparable size on SDS-PAGE and similar elution profiles to the wild-type. As a proof-of-concept, fluorescence dyes were conjugated either non-specifically to the wild-type antibody or site-specifically to the variants. Ongoing studies are exploring the potential application of these variants for conjugation with various therapeutic molecules.