ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, VIC, 3010, Australia.
Carbohydr Res. 2018 Jul 30;465:4-9. doi: 10.1016/j.carres.2018.05.008. Epub 2018 May 23.
Many monoclonal antibodies (mAbs) used in cancer immunotherapy mediate tumour cell lysis by recruiting natural killer (NK) cells; a phenomenon known as antibody-dependent cellular cytotoxicity (ADCC). Eliminating core-fucose from the N-glycans of a mAb enhances its capacity to induce ADCC. As such, inhibitors of fucosylation are highly desirable for the production of mAbs for research and therapeutic use. Herein, we describe a simple synthesis of 6,6,6-trifluoro-l-fucose (F3Fuc), a metabolic inhibitor of fucosylation, and demonstrate the utility of this molecule in the production of low-fucose mAbs from murine hybridoma cell lines.
许多用于癌症免疫治疗的单克隆抗体（mAbs）通过招募自然杀伤（NK）细胞介导肿瘤细胞裂解；这一现象被称为抗体依赖性细胞毒性（ADCC）。消除 mAb 中的 N-糖链核心岩藻糖可增强其诱导 ADCC 的能力。因此，用于研究和治疗用途的 mAb 生产非常需要岩藻糖基转移酶抑制剂。本文描述了 6,6,6-三氟-L-岩藻糖（F3Fuc）的简单合成方法，这是一种岩藻糖基化的代谢抑制剂，并展示了该分子在生产低岩藻糖 mAb 方面的应用，该 mAb 来自鼠杂交瘤细胞系。
