A Chemical Approach for Programmable Protein Outputs Based on Engineered Cell Interactions
| العنوان: | A Chemical Approach for Programmable Protein Outputs Based on Engineered Cell Interactions |
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| المؤلفون: | Andrew Ruff, Daniel A. Jacome, Justin D. Northrup, Sean W Reilly, Mark A. Sellmyer, Gabrielle S Blizard, Iris Lee |
| المصدر: | ACS Chem Biol |
| بيانات النشر: | American Chemical Society (ACS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell, Cell Communication, Computational biology, 01 natural sciences, Biochemistry, Trimethoprim, Article, Protein expression, Small Molecule Libraries, 03 medical and health sciences, Luciferases, Firefly, Proper function, medicine, Animals, Prodrugs, Cell Engineering, Dose-Response Relationship, Drug, 010405 organic chemistry, Activator (genetics), Proteins, General Medicine, Coculture Techniques, 0104 chemical sciences, 030104 developmental biology, medicine.anatomical_structure, Molecular Medicine, Intracellular |
| الوصف: | Cell-cell interactions and communication are crucial to the proper function of complex mammalian physiology including neurocognitive and immune system functions. While many tools are available for observing and perturbing intracellular processes, relatively few exist to probe intercellular processes. Current techniques for studying interactions often rely on direct protein contact, and few can manipulate diverse, functional outputs with tunable protein expression. To address these limitations, we have developed a small-molecule approach based on a trimethoprim prodrug-enzyme pair capable of reporting the presence of two different engineered cell populations with programmable protein outputs. The approach relies on bacterial nitroreductase enzyme catalysis, which is orthogonal to normal mammalian biology, and diffusion of trimethoprim from "activator" cells to "receiver" cells. We test this strategy, which can theoretically regulate many different types of proteins, using biochemical and in vitro culture assays with optical and cytokine protein readouts. This describes the first small-molecule approach capable of detecting and controlling engineered cell-cell outputs, and we anticipate future applications that are especially relevant to the field of immuno-oncology. |
| تدمد: | 1554-8937 1554-8929 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4176866dffb6233b6ec8e8cfaf8efe2d https://doi.org/10.1021/acschembio.0c00935 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4176866dffb6233b6ec8e8cfaf8efe2d |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15548937 15548929 |
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