Bioorthogonal Reaction of o-Quinone with Furan-2(3H)-One for Site-Selective Tyrosine Conjugation and Construction of Bispecific Antibody Complexes.

ABSTRACT: Bioorthogonal reactions enable the chemical conjugation of functional moieties to native proteins and empower the development of new diagnostic tools and therapeutics. Through site-selective reactions, therapeutic molecules can be conjugated with antibodies in a stoichiometry- and site-controlled manner. Here, a one-pot chemoenzymatic reaction is reported that preferentially modifies a terminal tyrosine of recombinant proteins, or tyrosine 296 in the Fc domain of selected human antibodies. This reaction combines tyrosinase-catalyzed oxidation of phenol to o-quinone, the bioorthogonal addition reaction of o-quinone with an azide-containing furan-2(3H)-one (FuA) moiety, and the subsequent azide click reactions. To this surprise, experimental evidence indicates that the o-quinone-FuA reaction

SUBMITTER: Chen H 

PROVIDER: S-EPMC12165061 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature