Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast
| Autor: | Elizabeth Bilsland, Harry J. Moss, Pınar Pir, Douglas B. Kell, Karin Lanthaler, Paul D. Dobson, Stephen G. Oliver |
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| Přispěvatelé: | Oliver, Stephen [0000-0001-6330-7526], Apollo - University of Cambridge Repository |
| Rok vydání: | 2011 |
| Předmět: |
Cell Membrane Permeability
Physiology Saccharomyces cerevisiae Drug Evaluation Preclinical Genomics Model system Plant Science Computational biology Genome Polymerase Chain Reaction General Biochemistry Genetics and Molecular Biology Yeast gene Cell membrane 03 medical and health sciences Canavanine 0302 clinical medicine Structural Biology medicine Humans lcsh:QH301-705.5 Ecology Evolution Behavior and Systematics 030304 developmental biology Genetics 0303 health sciences Agricultural and Biological Sciences(all) biology Biochemistry Genetics and Molecular Biology(all) Membrane transport protein Cell Membrane Membrane Transport Proteins Biological Transport Cell Biology biology.organism_classification Yeast medicine.anatomical_structure lcsh:Biology (General) Pharmaceutical Preparations 030220 oncology & carcinogenesis biology.protein General Agricultural and Biological Sciences Gene Deletion Research Article Developmental Biology Biotechnology Genome-Wide Association Study |
| Zdroj: | BMC Biology, Vol 9, Iss 1, p 70 (2011) BMC Biology |
| Popis: | Background The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. Results To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. Conclusions As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs. |
| Databáze: | OpenAIRE |
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