Tyrosinase-Mediated Synthesis of Nanobody-Cell Conjugates.
Johnathan C MazaDerek M García-AlmedinaLydia E BoikeNoah X HamlishDaniel K NomuraMatthew B FrancisPublished in: ACS central science (2022)
A convenient enzymatic strategy is reported for the modification of cell surfaces. Using a tyrosinase enzyme isolated from Agaricus bisporus , unique tyrosine residues introduced at the C-termini of nanobodies can be site-selectively oxidized to reactive o -quinones. These reactive intermediates undergo rapid modification with nucleophilic thiol, amine, and imidazole residues present on cell surfaces, producing novel nanobody-cell conjugates that display targeted antigen binding. We extend this approach toward the synthesis of nanobody-NK cell conjugates for targeted immunotherapy applications. The resulting NK cell conjugates exhibit targeted cell binding and elicit targeted cell death.