Conjugating proteins through covalent bonds that are not amide bonds or disulfides is not trivial.For example,nucleophiles (such as the ε-amino group of lysine and thiol group of cysteine) are prevalent on the surface of proteins.Although these residues are amenable to undergo SN2 reactions,controlling the stoichiometry and specificity of the bioconjugation reactions at these nucleophilic sites is difficult.In contrast to the traditional bioconjugation reactions solely driven by chemical reactivity,we implemented the general principle "affinity-guided reactivity" to harness nucleophilic reactions under physiological condition.