title: The end game of chemical genetics: target identification.
abstract: The use of classical genetic and molecular biology methods along with the sequencing of many genomes has proven crucial for elucidating complex biological processes. Despite being invaluable tools, their limitations have led to a search for more versatile alternatives and, thus, to the use of small molecules. Chemical genetics is a rapidly emerging field that uses small-molecule techniques to probe biological systems and is composed of three parts: natural product or small-molecule libraries, phenotypic screening and target identification. Currently, the biggest hurdle in the overall process of chemical genetics is target identification. Efforts to overcome this obstacle have led to advances in the areas of affinity chromatography, yeast haploinsufficiency, complementary DNA (cDNA) overexpression, DNA microarray, small-molecule microarray and RNA interference (RNAi) technologies. While these technologies continue to undergo further optimization, they have been integral in the identification and/or confirmation of many cellular targets and have seen an increase in applications to the drug-development process.
authors.affiliation: Department of Chemistry, Duke University, Durham, NC 27708, USA.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Kasper
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Baker
authors.forename: Hyoungsu
authors.initials: H
authors.lastname: Kim
authors.forename: Jiyong
authors.initials: J
authors.lastname: Hong
mesh_terms: D002846:Chromatography, Affinity / Q000379:methods; D020869:Gene Expression Profiling; D057895:Haploinsufficiency; D046228:Microarray Analysis / Q000379:methods; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011506:Proteins; D054852:Small Molecule Libraries