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Tyrosinase-Mediated Synthesis of Nanobody–Cell Conjugates
ACS Central Science ( IF 12.7 ) Pub Date : 2022-06-22 , DOI: 10.1021/acscentsci.1c01265
Johnathan C Maza 1 , Derek M García-Almedina 1 , Lydia E Boike 1, 2 , Noah X Hamlish 3 , Daniel K Nomura 1, 2, 3, 4, 5 , Matthew B Francis 1, 6
Affiliation  

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.

中文翻译:

酪氨酸酶介导的纳米抗体-细胞偶联物合成

据报道,一种方便的酶促策略可用于修饰细胞表面。使用从双孢蘑菇中分离的酪氨酸酶,在纳米抗体 C 末端引入的独特酪氨酸残基可以被选择性地氧化为反应性醌。这些反应性中间体经过细胞表面存在的亲核硫醇、胺和咪唑残基的快速修饰,产生了显示靶向抗原结合的新型纳米抗体-细胞偶联物。我们将这种方法扩展到用于靶向免疫治疗应用的纳米抗体-NK 细胞偶联物的合成。得到的 NK 细胞偶联物表现出靶向细胞结合并引发靶向细胞死亡。
更新日期:2022-06-22
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