Article ; Online: A Chemical Approach for Programmable Protein Outputs Based on Engineered Cell Interactions.
ACS chemical biology
2020 Volume 16, Issue 1, Page(s) 52–57
Abstract: 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, ... ...
| Abstract | 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 |
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| MeSH term(s) | Animals ; Cell Communication ; Cell Engineering ; Coculture Techniques ; Dose-Response Relationship, Drug ; Luciferases, Firefly/chemistry ; Prodrugs/chemistry ; Proteins/chemistry ; Small Molecule Libraries/chemistry ; Trimethoprim/chemistry |
| Chemical Substances | Prodrugs ; Proteins ; Small Molecule Libraries ; Trimethoprim (AN164J8Y0X) ; Luciferases, Firefly (EC 1.13.12.7) |
| Language | English |
| Publishing date | 2020-12-22 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 1554-8937 |
| ISSN (online) | 1554-8937 |
| DOI | 10.1021/acschembio.0c00935 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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