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Chemical Genetics
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is Chemical Genetics?
Chemical genetics involves the screening of small molecules for their interactions with proteins within cells. This approach can be used in both forward(find a protein using effect of small molecule) or reverse (find a small molecule that targets a particular protein) manners(1). Current microarray technology allows for the screening of large numbers of molecules in a time efficient manner(2, see video below). An appeal of the chemical genetics approach is that small molecules that are found to affect particular proteins make good drug candidates(3).
Chemical Genetics of Nephrogenic Diabetes Insipidus
Compounds that have been tested to treat a particular disease or target a particular protein can be determined by using the PubChem database(4). No compounds have been tested to targeted AQP2 specifically, however the compound Relcovaptan has decreased urine output in individuals with nephrogenic diabetes insipidus caused by defects in the vasopressin receptor(5).
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Discussion
The current lack of compounds targeting AQP2 specifically likely reflects the rarity of AQP2-associated nephrogenic diabetes insipidus.The only aquaporin gene that has been used as a drug target is AQP4, and all known compounds that affect it are inhibitory(6). Thus, significantly more research needs to be done on AQP2 as a drug target for treatment of nephrogenic diabetes insipidus.
Works Cited
1.Stockwell, B. R. (2000). Chemical genetics: Ligand-based discovery of gene function. Nature Reviews Genetics, 1(2), 116-125. doi:10.1038/35038557
2. Small-Molecule Microarrays. http://www.hhmi.org/biointeractive/small-molecule-microarrays. Accessed April 10, 2017.
3.Stockwell, B. R. (2004). Exploring biology with small organic molecules. Nature, 432(7019), 846-854. doi:10.1038/nature03196
4.Pubchem. https://pubchem.ncbi.nlm.nih.gov/search/. Accessed April 10, 2017.
5.Gavrin, L. K., Denny, R. A., & Saiah, E. (2012). Small Molecules That Target Protein Misfolding. Journal of Medicinal Chemistry, 55(24), 10823-10843. doi:10.1021/jm301182j
6.Aqp4. https://pubchem.ncbi.nlm.nih.gov/target/gene/11829#section=Top. Accessed April 10,2017.
2. Small-Molecule Microarrays. http://www.hhmi.org/biointeractive/small-molecule-microarrays. Accessed April 10, 2017.
3.Stockwell, B. R. (2004). Exploring biology with small organic molecules. Nature, 432(7019), 846-854. doi:10.1038/nature03196
4.Pubchem. https://pubchem.ncbi.nlm.nih.gov/search/. Accessed April 10, 2017.
5.Gavrin, L. K., Denny, R. A., & Saiah, E. (2012). Small Molecules That Target Protein Misfolding. Journal of Medicinal Chemistry, 55(24), 10823-10843. doi:10.1021/jm301182j
6.Aqp4. https://pubchem.ncbi.nlm.nih.gov/target/gene/11829#section=Top. Accessed April 10,2017.