{{Chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 400128403 | ImageFile = Lactacystin.svg | ImageFile_Ref = {{chemboximage|correct|??}} | ImageSize = 244 | ImageName = Stereo skeletal formula of lactacystin ((2''R'')-2-amid, (2''R'',3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth) | SystematicName = (2''R'')-2-Acetamido-3-({(2''R'',3''S'',4''R'')-3-hydroxy-2-[(1''S'')-1-hydroxy-2-methylpropyl]-4-methyl-5-oxopyrrolidine-2-carbonyl}sulfanyl)propanoic acid |Section1={{Chembox Identifiers | CASNo = 133343-34-7 | CASNo_Ref = {{cascite|correct|??}} | PubChem = 3870 | PubChem1 = | PubChem1_Comment = <small>-2-((1''S'')-1-hydrox)prop</small> | PubChem2 = 45039639 | PubChem2_Comment = <small>(3''S'',4''R'')-3-hydrox,-2-((1''R'')-1-hydrox)prop,-4-meth</small> | PubChem3 = 46782036 | PubChem3_Comment = <small>(2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''R'')-1-hydrox)prop,-4-meth</small> | PubChem4 = 3034764 | PubChem4_Comment = <small>(2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth</small> | ChemSpiderID = 3735 | ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID1 = 2299173 | ChemSpiderID1_Ref = {{chemspidercite|changed|chemspider}} | ChemSpiderID1_Comment = <small>(2''R'')-2-amid, (3''S'',4''R'')-3-hydrox,-2-((1''S'')-1-hydrox)prop,-4-meth</small> | MeSHName = Lactacystin | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 52722 | ChEMBL = 374308 | ChEMBL_Ref = {{ebicite|changed|EBI}} | SMILES = CC(C)C(O)C1(NC(=O)C(C)C1O)C(=O)SCC(NC(C)=O)C(O)=O | SMILES1 = CC(=O)NC(CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O)C(=O)O | SMILES2 = OC1C(C)C(=O)NC1(C(=O)SCC(NC(C)=O)C(O)=O)C(O)C(C)C | StdInChI = 1S/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23) | StdInChI_Ref = {{stdinchicite|changed|chemspider}} | InChI = 1/C15H24N2O7S/c1-6(2)10(19)15(11(20)7(3)12(21)17-15)14(24)25-5-9(13(22)23)16-8(4)18/h6-7,9-11,19-20H,5H2,1-4H3,(H,16,18)(H,17,21)(H,22,23) | StdInChIKey = DAQAKHDKYAWHCG-UHFFFAOYSA-N | StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} | InChIKey = DAQAKHDKYAWHCG-WBMULXAQBF }} |Section2={{Chembox Properties | C=15 | H=24 | N=2 | O=7 | S=1 | LogP = 0.086 | pKa = 3.106 | pKb = 10.891 }} }}
'''Lactacystin''' is an organic compound naturally synthesized by bacteria of the genus ''Streptomyces'' first identified as an inducer of neuritogenesis in neuroblastoma cells in 1991.<ref name="Omura">Omura S, Fujimoto T, Otoguro K, Matsuzaki K, Moriguchi R, Tanaka H, Sasaki Y. (1991). Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells: S. Omura, et al. ''J. Antibiot.'' 44(1):113-6.</ref> The target of lactacystin was subsequently found to be the proteasome on the basis of its affinity for certain catalytic subunits of the proteasome by Fenteany and co-workers in 1995.<ref name="Fenteany1">{{cite journal |vauthors=Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL |title=Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin |journal=Science |volume=268 |issue=5211 |pages=726–31 |year=1995 |pmid=7732382 |doi=10.1126/science.7732382|bibcode=1995Sci...268..726F |s2cid=37779687 }}</ref> The proteasome is a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. Lactacystin was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. The transformation product of lactacystin clasto-lactacystin β-lactone (also known as omuralide) covalently modifies the amino-terminal threonine of specific catalytic subunits of the proteasome, a discovery that helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal threonine protease. The molecule is commonly used in biochemistry and cell biology laboratories as a selective inhibitor of the proteasome.<ref name="Fenteany1">{{cite journal |vauthors=Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL |title=Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin |journal=Science |volume=268 |issue=5211 |pages=726–31 |year=1995 |pmid=7732382 |doi=10.1126/science.7732382|bibcode=1995Sci...268..726F |s2cid=37779687 }}</ref><ref name="Fenteany2">{{cite journal |vauthors=Fenteany G, Schreiber SL |title=Lactacystin, proteasome function, and cell fate |journal=J. Biol. Chem. |volume=273 |issue=15 |pages=8545–8 |year=1998 |pmid= 9535824 |doi=10.1074/jbc.273.15.8545|doi-access= free}}</ref> The first total synthesis of lactacystin was developed in 1992 by Corey and Reichard,<ref name="Corey">''"Total Synthesis of Lactacystin"'' Corey, E. J.; Reichard, G. A. ''J. Am. Chem. Soc.'' '''1992''', ''114'', 10677.</ref> and a number of other syntheses of this molecule have also been published. There are more than 1,660 entries for lactacystin in PubMed as of January 2019.
==See also== *Satoshi Ōmura
==References== {{Reflist}}
Category:Acetamides Category:Pyrrolidones Category:Secondary alcohols Category:Total synthesis Category:Lactams