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Cycloheximide

Cycloheximide
Cycloheximide
Names
Preferred IUPAC name
4-{(2R)-2-[(1S,3S,5S)-3,5-Dimethyl-2-oxocyclohexyl]-2-hydroxyethyl}piperidine-2,6-dione
Other names
Naramycin A, hizarocin, actidione, actispray, kaken, U-4527
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.578 Edit this at Wikidata
KEGG
RTECS number
  • MA4375000
UNII
  • InChI=1S/C15H23NO4/c1-8-3-9(2)15(20)11(4-8)12(17)5-10-6-13(18)16-14(19)7-10/h8-12,17H,3-7H2,1-2H3,(H,16,18,19)/t8-,9-,11-,12+/m0/s1 checkY
    Key: YPHMISFOHDHNIV-FSZOTQKASA-N checkY
  • InChI=1/C15H23NO4/c1-8-3-9(2)15(20)11(4-8)12(17)5-10-6-13(18)16-14(19)7-10/h8-12,17H,3-7H2,1-2H3,(H,16,18,19)/t8-,9-,11-,12+/m0/s1
    Key: YPHMISFOHDHNIV-FSZOTQKABD
  • O=C2NC(=O)CC(C[C@@H](O)[C@H]1C(=O)[C@@H](C)C[C@H](C)C1)C2
Properties
C15H23NO4
Molar mass 281.352 g·mol−1
Appearance Colorless crystals
Melting point 119.5 to 121 °C (247.1 to 249.8 °F; 392.6 to 394.1 K)
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Highly toxic
GHS labelling:
GHS06: Toxic
Safety data sheet (SDS) Oxford MSDS
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 ?)

Cycloheximide is a naturally occurring fungicide produced by the bacterium Streptomyces griseus. Cycloheximide exerts its effects by interfering with the translocation step in protein synthesis (movement of two tRNA molecules and mRNA in relation to the ribosome), thus blocking eukaryotic translational elongation. Cycloheximide is widely used in biomedical research to inhibit protein synthesis in eukaryotic cells studied in vitro (i.e. outside of organisms). It is inexpensive and works rapidly. Its effects are rapidly reversed by simply removing it from the culture medium.[1]

Due to significant toxic side effects, including DNA damage, teratogenesis, and other reproductive effects (including birth defects and toxicity to sperm[2]), cycloheximide is generally used only in in vitro research applications, and is not suitable for human use as a therapeutic compound. Although it has been used as a fungicide in agricultural applications, this application is now decreasing as the health risks have become better understood.

Because cycloheximide rapidly breaks down in a basic environment, decontamination of work surfaces and containers can be achieved by washing with a non-harmful alkali solution such as soapy water or aqueous sodium bicarbonate.

It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.[3]

Discovery

Cycloheximide was reported in 1946 by Alma Joslyn Whiffen-Barksdale at the Upjohn Company.[4]

Experimental applications

Cycloheximide can be used as an experimental tool in molecular biology to determine the half-life of a protein. Treating cells with cycloheximide in a time-course experiment followed by western blotting of the cell lysates for the protein of interest can show differences in protein half-life. Cycloheximide treatment provides the ability to observe the half-life of a protein without confounding contributions from transcription or translation. Irreversible analogues of cycloheximide have also been reported.[5]

Mitochondrial protein synthesis is resistant to inhibition by cycloheximide. On the other hand chloramphenicol inhibits mitochondrial (and bacterial) protein synthesis, but synthesis on cytoplasmic ribosomes is resistant. Before genomes were available, these inhibitors were used to determine which mitochondrial proteins were synthesized in the mitochondria from mitochondrial genes.[6][7]

Cycloheximide is used as a plant growth regulator to stimulate ethylene production. It is used as a rodenticide [citation needed] and other animal pesticide. It is also used in media to detect unwanted bacteria in beer fermentation by suppressing yeasts and molds growth in test medium.

The translational elongation freezing properties of cycloheximide are also used for ribosome profiling / translational profiling. Translation is halted via the addition of cycloheximide, and the DNA/RNA in the cell is then nuclease treated. The ribosome-bound parts of RNA can then be sequenced.

Cycloheximide has also been used to make isolation of bacteria from environmental samples easier.[8]

Spectrum of fungal susceptibility

Cycloheximide has been used to isolate dermatophytes and inhibit the growth of fungi in brewing test media. The following represents susceptibility data for a few commonly targeted fungi:[9]

See also

References

  1. ^ Müller, Franz; Ackermann, Peter; Margot, Paul (2012). "Fungicides, Agricultural, 2. Individual Fungicides". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.o12_o06. ISBN 978-3527306732.
  2. ^ "TOXNET". toxnet.nlm.nih.gov. Archived from the original on 2007-05-22. Retrieved 2007-05-03.
  3. ^ "40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities" (PDF). Code of Federal Regulations (July 1, 2008 ed.). Government Printing Office. Archived from the original (PDF) on February 25, 2012. Retrieved October 29, 2011.
  4. ^ New York Botanical Gardens. "Alma Whiffen Barksdale Records (RG5)". nybg.org. Retrieved 1 March 2017.
  5. ^ Park, Yongho; Koga, Yumi; Su, Cindy; Waterbury, Amanda L.; Johnny, Christopher L.; Liau, Brian B. (2019-04-08). "Versatile Synthetic Route to Cycloheximide and Analogues That Potently Inhibit Translation Elongation". Angewandte Chemie International Edition. 58 (16): 5387–5391. doi:10.1002/anie.201901386. ISSN 1433-7851. PMID 30802354.
  6. ^ Weiss H, Sebald W, and Bücher T (1971). "Cycloheximide resistant incorporation of amino acids into a polypeptide of the cytochrome oxidase of Neurospora crassa" (PDF). Eur. J. Biochem. 22 (1): 19–26. doi:10.1111/j.1432-1033.1971.tb01509.x. PMID 4329217.
  7. ^ Sebald W, Weiss H, and Jackl G (1972). "Inhibition of the Assembly of Cytochrome Oxidase in Neurospora crassa by Chloramphenicol". Eur. J. Biochem. 30 (3): 413–417. doi:10.1111/j.1432-1033.1972.tb02112.x. PMID 4344826.
  8. ^ Sands, D. C.; Rovira, A. D. (September 1970). "Isolation of Fluorescent Pseudomonads with a Selective Medium". Applied Microbiology. 20 (3): 513–514. doi:10.1128/am.20.3.513-514.1970. ISSN 0003-6919. PMC 376970. PMID 16349887.
  9. ^ "Cycloheximide – The Antimicrobial Index Knowledgebase – TOKU-E". antibiotics.toku-e.com.
Quelle: https://en.wikipedia.org/wiki/Cycloheximide