Page 121 - Tyrosine-Based Bioconjugations - Jorick Bruins

based labeling can be insured after the antibody binds the target (Figure 4B).28 In the case of antibodies with an exposed tyrosine residue on the CDR-H3, as with AT1413, this can be more easily achieved via the selective oxidation to the DOPA-moiety via mTyr and ascorbic acid.29 The DOPA-moiety can then selectively be oxidized to the quinone by electrochemistry30 or sodium periodate,7 allowing for nucleophilic amino acids to perform Michael addition on the CDR- located quinone (Figure 4C). By doing either the photoaffinity labeling, or the electrochemistry labeling, detailed information about the epitope of these antibodies can be achieved.
Figure 4. (A) Proposed structure of BCN-diazirine bifunctional molecule (9). (B) Covalent antigen binding via introduction of diazirine and subsequent photolabeling. (C) Covalent antigen binding via DOPA-formation and subsequent oxidation.
Altogether, there are many applications for SPOCQ to contribute in the field of bioconjugate chemistry. Its mild conditions and selective nature allows for the modification of proteins in an inducible fashion, and it has proven capable of creating conjugates for the next generation of antibody-drug conjugates and immunotherapies.
Summary and General Discussion
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