Coupling of Immunostimulants to Live Cells through Metabolic Glycoengineering and Bioorthogonal Click Chemistry
| Autor: | Aline Mongis, Friedrich Piller, Véronique Piller |
|---|---|
| Přispěvatelé: | Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycan Cell Survival [SDV]Life Sciences [q-bio] Biomedical Engineering Pharmaceutical Science Bioengineering 01 natural sciences 03 medical and health sciences Mice Immune system Adjuvants Immunologic Polysaccharides Cell Line Tumor Neoplasms Animals Viability assay Pharmacology biology 010405 organic chemistry Chemistry Oligonucleotide Macrophages Organic Chemistry Macrophage Activation 0104 chemical sciences 3. Good health Mice Inbred C57BL 030104 developmental biology CpG site Biochemistry Oligodeoxyribonucleotides Cell culture biology.protein Click chemistry Click Chemistry Bioorthogonal chemistry Biotechnology |
| Zdroj: | Bioconjugate Chemistry Bioconjugate Chemistry, American Chemical Society, 2017, 28 (4), pp.1151-1165. ⟨10.1021/acs.bioconjchem.7b00042⟩ |
| ISSN: | 1043-1802 1520-4812 |
| Popis: | International audience; 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 Ac4Ga1NAz 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 control 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. |
| Databáze: | OpenAIRE |
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