4-(2,5-Dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide improves monoclonal antibody production in a Chinese hamster ovary cell culture
| Autor: | Koichi Nonaka, Hirofumi Kakihara, Yuichi Aki, Kenshu Fujiwara, Yuta Katsumata |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0106 biological sciences
Cell Culture Techniques Biochemistry 01 natural sciences law.invention chemistry.chemical_compound Adenosine Triphosphate Glucose Metabolism law Benzamide 0303 health sciences Multidisciplinary biology Organic Compounds Chinese hamster ovary cell Monosaccharides Antibodies Monoclonal Chemistry Metabolic Engineering Cell Processes Benzamides Physical Sciences Recombinant DNA Carbohydrate Metabolism Medicine Biological Cultures Batch Culture Antibody Production Signal Transduction Research Article Cell Culturing Techniques Glycan Monoclonal Antibody Production Cell Survival medicine.drug_class Science Carbohydrates CHO Cells Library Screening Research and Analysis Methods Monoclonal antibody Cell Growth Structure-Activity Relationship 03 medical and health sciences Cricetulus Polysaccharides 010608 biotechnology medicine Animals Pyrroles Molecular Biology Techniques Molecular Biology Cell Proliferation 030304 developmental biology Molecular Biology Assays and Analysis Techniques Cell growth Dimethyl sulfoxide Organic Chemistry Chemical Compounds Galactose Biology and Life Sciences Cell Biology Cell Cultures Culture Media Glucose Metabolism chemistry Cell culture Immunologic Techniques biology.protein |
| Zdroj: | PLoS ONE, Vol 16, Iss 4, p e0250416 (2021) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0250416 |
| Popis: | There is a continuous demand to improve monoclonal antibody production for medication supply and medical cost reduction. For over 20 years, recombinant Chinese hamster ovary cells have been used as a host in monoclonal antibody production due to robustness, high productivity and ability to produce proteins with ideal glycans. Chemical compounds, such as dimethyl sulfoxide, lithium chloride, and butyric acid, have been shown to improve monoclonal antibody production in mammalian cell cultures. In this study, we aimed to discover new chemical compounds that can improve cell-specific antibody production in recombinant Chinese hamster ovary cells. Out of the 23,227 chemicals screened in this study, 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide was found to increase monoclonal antibody production. The compound suppressed cell growth and increased both cell-specific glucose uptake rate and the amount of intracellular adenosine triphosphate during monoclonal antibody production. In addition, the compound also suppressed the galactosylation on a monoclonal antibody, which is a critical quality attribute of therapeutic monoclonal antibodies. Therefore, the compound might also be used to control the level of the galactosylation for the N-linked glycans. Further, the structure-activity relationship study revealed that 2,5-dimethylpyrrole was the most effective partial structure of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide on monoclonal antibody production. Further structural optimization of 2,5-dimethylpyrrole derivatives could lead to improved production and quality control of monoclonal antibodies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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