Maza Johnathan C, García-Almedina Derek M, Boike Lydia E, Hamlish Noah X, Nomura Daniel K, Francis Matthew B
Department of Chemistry, University of California, Berkeley, California 94720, United States.
Novartis-Berkeley Center for Proteomics and Chemistry Technologies, Cambridge, Massachusetts 02139, United States.
ACS Cent Sci. 2022 Jul 27;8(7):955-962. doi: 10.1021/acscentsci.1c01265. Epub 2022 Jun 22.
A convenient enzymatic strategy is reported for the modification of cell surfaces. Using a tyrosinase enzyme isolated from , unique tyrosine residues introduced at the C-termini of nanobodies can be site-selectively oxidized to reactive -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.
报道了一种用于修饰细胞表面的便捷酶促策略。利用从[具体来源未给出]分离出的酪氨酸酶，在纳米抗体C末端引入的独特酪氨酸残基可被位点选择性氧化为活性醌。这些活性中间体与细胞表面存在的亲核硫醇、胺和咪唑残基快速发生修饰反应，生成具有靶向抗原结合能力的新型纳米抗体-细胞缀合物。我们将此方法扩展至用于靶向免疫治疗应用的纳米抗体-NK细胞缀合物的合成。所得的NK细胞缀合物表现出靶向细胞结合并引发靶向细胞死亡。
