生物正交化学
化学
点击化学
聚糖
生物化学
免疫系统
共价键
细胞培养
细胞
分子生物学
组合化学
免疫学
生物
遗传学
糖蛋白
有机化学
作者
Aline Mongis,Friedrich Piller,Véronique Piller
标识
DOI:10.1021/acs.bioconjchem.7b00042
摘要
The present study investigated the potential of metabolic glycoengineering followed by bioorthogonal click chemistry for introducing into cell-surface glycans different immunomodulating molecules. Mouse tumor models EG7 and MC38-OVA were treated with Ac4GalNAz and Ac4ManNAz followed by ligation of immunostimulants to modified cell-surface glycans of the living cells through bioorthogonal click chemistry. The presence of covalently bound oligosaccharide and oligonucleotide immunostimulants could be clearly established. The activation of a reporter macrophage cell line was determined. Depending on the tumor cell line, covalently and noncovalently bound CpG activated the macrophages by between 67 and 100% over controls. EG7 cells with covalently attached immunostimulants and controls were injected subcutaneously into C57BL/6 mice. All tumor cells subjected to the complete treatment with control molecules formed tumors like nontreated cells confirming cell viability. However, when CpG oligonucleotide was linked to cell-surface glycans, tumor growth was slowed significantly (60% reduction, n = 10, by covalently bound CpG compared to noncovalently bound CpG, n = 10). When mice that had not developed large tumors were challenged with unmodified EG7 cells, no new tumors developed, suggesting protection through the immune system.
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