Lactacystin

Lactacystin
Names
IUPAC name
2-(acetylamino)-3-[({3-hydroxy-2-[1-hydroxy-2-methylpropyl]-4-methyl-5-oxopyrrolidin-2-yl}carbonyl)sulfanyl]propanoic acid
Identifiers
133343-34-7 YesY
ChEBI CHEBI:52722 N
ChEMBL ChEMBL374308 N
ChemSpider 3735 N
2299173 (2R)-2-amid, (3S,4R)-3-hydrox,-2-((1S)-1-hydrox)prop,-4-meth N
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Image
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MeSH Lactacystin
PubChem 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
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).
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Infobox references

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 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.

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. 1 2 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: 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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