Lactacystin

Structural formula
General
Surname	Lactacystin
Molecular formula	C 15 H 24 N 2 O 7 S
External identifiers / databases
PubChem	3034764
ChemSpider	2299173
Wikidata	Q6468907
properties
Molar mass	376.43 g mol −1
Physical state	firmly
safety instructions
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lactacystin is an organic compound that is synthesized by bacteria of the genus Streptomyces and was first described in 1991.

effect

Lactacystin is a proteasome inhibitor and inhibits specific catalytic subunits of the proteasome. Proteasome is an enzyme that breaks down proteins intracellularly and belongs to the peptidases . It thus takes part in the regulation of the cell cycle. The control of the proteasome function is therefore potentially suitable for cancer therapy. Lactacystin was the first non-peptide proteasome inhibitor and is now widely used in biochemistry and cell biology .

synthesis

The first total synthesis of lactacystin was developed by EJ Corey in 1992 and was later supplemented by an efficient and direct enantioselective synthesis. In the meantime, various research groups have developed alternative syntheses.

Individual evidence

↑ ^a ^b Lactacystin data sheet , ≥90% (HPLC) from Sigma-Aldrich , accessed on December 28, 2013 ( PDF ).
↑ S. Omura, K. Matsuzaki et al. a .: Structure of lactacystin, a new microbial metabolite which induces differentiation of neuroblastoma cells. In: The Journal of antibiotics. Volume 44, Number 1, January 1991, pp. 117-118, PMID 2001981 .
↑ G. Fenteany, R. Standaert, W. Lane, S. Choi, EJ Corey, S. Schreiber: Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. In: Science. 268, 1995, pp. 726-731, doi : 10.1126 / science.7732382 .
^ Do Hee Lee, Alfred L. Goldberg: Proteasome inhibitors: valuable new tools for cell biologists. In: Trends in cell biology 8.10 (1998): pp. 397-403 doi : 10.1016 / S0962-8924 (98) 01346-4 .
↑ EJ Corey, Gregory A. Reichard: Total synthesis of lactacystin. In: Journal of the American Chemical Society. 114, 1992, pp. 10677-10678, doi : 10.1021 / ja00052a096 .
↑ EJ Corey, Weidong Li, Tohru Nagamitsu: An efficient and concise enantioselective total synthesis of lactacystin. In: Angewandte Chemie 110.12 (1998): pp. 1784–1787. doi : 10.1002 / (SICI) 1521-3757 (19980619) 110: 12 <1784 :: AID-ANGE1784> 3.0.CO; 2- #
↑ Nobuhisa Fukuda, Kazuki Sasaki, TVRS Sastry, Motomu Kanai, Masakatsu Shibasaki: Catalytic Asymmetric Total Synthesis of (+) - Lactacystin. In: The Journal of Organic Chemistry. 71, 2006, pp. 1220-1225, doi : 10.1021 / jo0524223 .

[Sigma-1] Lactacystin data sheet , ≥90% (HPLC) from Sigma-Aldrich , accessed on December 28, 2013 ( PDF ).

[PMID2001981-2] S. Omura, K. Matsuzaki et al. a .: Structure of lactacystin, a new microbial metabolite which induces differentiation of neuroblastoma cells. In: The Journal of antibiotics. Volume 44, Number 1, January 1991, pp. 117-118, PMID 2001981 .

[3] G. Fenteany, R. Standaert, W. Lane, S. Choi, EJ Corey, S. Schreiber: Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. In: Science. 268, 1995, pp. 726-731, doi : 10.1126 / science.7732382 .

[4] Do Hee Lee, Alfred L. Goldberg: Proteasome inhibitors: valuable new tools for cell biologists. In: Trends in cell biology 8.10 (1998): pp. 397-403 doi : 10.1016 / S0962-8924 (98) 01346-4 .

[5] EJ Corey, Gregory A. Reichard: Total synthesis of lactacystin. In: Journal of the American Chemical Society. 114, 1992, pp. 10677-10678, doi : 10.1021 / ja00052a096 .

[6] EJ Corey, Weidong Li, Tohru Nagamitsu: An efficient and concise enantioselective total synthesis of lactacystin. In: Angewandte Chemie 110.12 (1998): pp. 1784–1787. doi : 10.1002 / (SICI) 1521-3757 (19980619) 110: 12 <1784 :: AID-ANGE1784> 3.0.CO; 2- #

[7] Nobuhisa Fukuda, Kazuki Sasaki, TVRS Sastry, Motomu Kanai, Masakatsu Shibasaki: Catalytic Asymmetric Total Synthesis of (+) - Lactacystin. In: The Journal of Organic Chemistry. 71, 2006, pp. 1220-1225, doi : 10.1021 / jo0524223 .