Chemical modifications of native proteins can facilitate production of supernatural protein functions that are not easily accessible by complementary methods relying on genetic manipulations. Even though precise control over the chemo-, site-, and modification-number-selectivity in protein chemical conjugates with maintained structural integrity and homogeneity is highly important, it still represents a formidable challenge. In 2016, we reported a transition metal-free method for tryptophan (Trp)-selective bioconjugation of proteins that operates under ambient conditions. This method exhibits low levels of crossreactivity and leaves higher-order structures of the protein and various functional groups therein unaffected. The strategy to target less abundant amino acids contributes to the formation of structurally homogeneous conjugates. Another advantageous characteristic of this novel bioconjugation is an absence of toxic metals and biochemically incompatible conditions, which easily find therapeutic applications. Recently, studies aiming at concise production of a homogeneous antibody-drug conjugate (ADC) using the Trp-selective bioconjugation are ongoing in our group. A Trp-conjugate of a model protein revealed physicochemical advantages over conventionally utilized lysine-conjugates. We would also like to present the recent progress about ADC development.
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