Lactacystin

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Lactacystin
Stereo skeletal formula of lactacystin ((2R)-2-amid, (2R,3S,4R)-3-hydrox,-2-((1S)-1-hydrox)prop,-4-meth)
Names
IUPAC name
2-(acetylamino)-3-[({3-hydroxy-2-[1-hydroxy-2-methylpropyl]-4-methyl-5-oxopyrrolidin-2-yl}carbonyl)sulfanyl]propanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
  • 3735 ☒N
  • 2299173 (2R)-2-amid, (3S,4R)-3-hydrox,-2-((1S)-1-hydrox)prop,-4-meth ☒N
MeSH Lactacystin
  • 3870
  • 45039639 (3S,4R)-3-hydrox,-2-((1R)-1-hydrox)prop,-4-meth
  • 46782036 (2R)-2-amid, (3S,4R)-3-hydrox,-2-((1R)-1-hydrox)prop,-4-meth
  • 3034764 (2R)-2-amid, (3S,4R)-3-hydrox,-2-((1S)-1-hydrox)prop,-4-meth
  • InChI=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) ☒N
    Key: DAQAKHDKYAWHCG-UHFFFAOYSA-N ☒N
  • 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)
    Key: DAQAKHDKYAWHCG-WBMULXAQBF
  • CC(C)C(O)C1(NC(=O)C(C)C1O)C(=O)SCC(NC(C)=O)C(O)=O
  • CC(=O)NC(CSC(=O)C1(C(O)C(C)C)NC(=O)C(C)C1O)C(=O)O
  • OC1C(C)C(=O)NC1(C(=O)SCC(NC(C)=O)C(O)=O)C(O)C(C)C
Properties
C15H24N2O7S
Molar mass 376.42 g·mol−1
log P 0.086
Acidity (pKa) 3.106
Basicity (pKb) 10.891
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Lactacystin is an organic compound naturally synthesized by bacteria of the genus Streptomyces first described in 1991.[1] The first total synthesis of lactacystin was developed by Elias Corey and Gregory Reichard in 1992.[2] Lactacystin binds and inhibits specific catalytic subunits of the proteasome,[3] a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. It was the first non-peptidic proteasome inhibitor discovered and is widely used as a research tool in biochemistry and cell biology. It covalently modifies the amino-terminal threonine of specific catalytic subunits of the proteasome, a discovery helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal threonine protease. The molecule is most commonly used as in biochemistry and cell biology laboratories as a selective inhibitor of the proteasome.[3][4] The molecule is a lactam, or cyclic amide. A number of syntheses of this molecule have been published and there are more than 1,500 citations for lactacystin in PubMed as of 2013.

See also

References

  1. ^ 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.
  2. ^ "Total Synthesis of Lactacystin" Corey, E. J.; Reichard, G. A. J. Am. Chem. Soc. 1992, 114, 10677.
  3. ^ a b Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ, Schreiber SL (1995). "Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin". Science. 268 (5211): 726–31. doi:10.1126/science.7732382. PMID 7732382.
  4. ^ Orlowski RZ. (1999). The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ 6: 303-313.
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