Maleimide– based conjugates have been shown to undergo retro– addition reactions in the presence of competing thiols. In serum, this can result in de– conjugation by exchange reactions with free thiol groups within circulating albumin. Maleimide, as well as other monoalkylation reagents also leave the cysteines from the original disulfides unbridged, introducing a potential for instability to the antibody. A promising solution to these problems is the utilization of bis– reactive bridging reagents that are able to restore a covalent linkage between the two cysteines. This approach uses bis– sulfone reagents that are selective for the cysteine sulfur atoms from a native disulfide that has been reduced.