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Title: Chemogenetics  
Author: World Heritage Encyclopedia
Language: English
Subject: Ki Database, Chemical engineering
Collection: Chemical Engineering
Publisher: World Heritage Encyclopedia


The term chemogenetics has been used to describe the processes by which macromolecules can be engineered to interact with previously unrecognized small molecules. Chemogenetics as a term was originally coined to describe the observed effects of mutations on chalcone isomerase activity on substrate specificities in the flowers of Dianthus caryophyllus.[1] Such engineered macromolecules include nucleic acid hybrids,[2] kinases [3] a variety of metabolic enzymes,[4][5] and G-protein coupled receptors (GPCRs) such as DREADDs.[6][7][8][9][10][11]


GPCRs are the target for some of the most widely used pharmaceuticals to treat diseases that involve virtually all tissues of the body. Viral expression of DREADD proteins, both in-vivo enhancers and inhibitors of neuronal function, have been used to bidirectionally control behaviors in mice (e.g odor discimination).[12]


  1. ^ Forkmann G, Dangelmayr B. 1980. Genetic control of chalcone isomerase activity in flowers of Dianthus caryophyllus. Biochem Genet 18: 519-27
  2. ^ Strobel SA, Ortoleva-Donnelly L, Ryder SP, Cate JH, Moncoeur E. 1998. Complementary sets of noncanonical base pairs mediate RNA helix packing in the group I intron active site. Nat Struct Biol 5: 60-
  3. ^ Bishop AC, Shah K, Liu Y, Witucki L, Kung C, Shokat KM. 1998. Design of allele-specific inhibitors to probe protein kinase signaling. Curr Biol 8: 257-66
  4. ^ Collot J, Gradinaru J, Humbert N, Skander M, Zocchi A, Ward TR. 2003. Artificial metalloenzymes for enantioselective catalysis based on biotin-avidin. J Am Chem Soc 125: 9030-1
  5. ^ Haring D, Distefano MD. 2001. Enzymes by design: chemogenetic assembly of transamination active sites containing lysine residues for covalent catalysis. Bioconjug Chem 12: 385-90
  6. ^ Strader CD, Gaffney T, Sugg EE, Candelore MR, Keys R, et al. 1991. Allele-specific activation of genetically engineered receptors. J Biol Chem 266: 5-8
  7. ^ Coward P, Wada HG, Falk MS, Chan SD, Meng F, et al. 1998. Controlling signaling with a specifically designed Gi-coupled receptor. Proc Natl Acad Sci U S A 95: 352-7
  8. ^ Westkaemper R, Glennon R, Hyde E, Choudhary M, Khan N, Roth B. 1999. Engineering in a region of bulk tolerance into the 5-HT2A receptor. Eur J Med Chem 34: 441-47
  9. ^ Jacobson KA, Gao ZG, Chen A, Barak D, Kim SA, et al. 2001. Neoceptor concept based on molecular complementarity in GPCRs: a mutant adenosine A(3) receptor with selectively enhanced affinity for amine-modified nucleosides. J Med Chem 44: 4125-36
  10. ^ Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL. 2007. Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci U S A 104: 5163-8
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