World Library  
Flag as Inappropriate
Email this Article

Spectinomycin

Article Id: WHEBN0005120442
Reproduction Date:

Title: Spectinomycin  
Author: World Heritage Encyclopedia
Language: English
Subject: Aminoglycoside, Antibiotics, Plant transformation vector, Spec, List of drugs: Sp-Sub
Collection:
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Spectinomycin

Spectinomycin
Systematic (IUPAC) name
(1R,3S,5R,8R,10R,11S,12S,13R,14S)-8,12,14-trihydroxy-5-methyl-11,13-bis(methylamino)-2,4,9-trioxatricyclo[8.4.0.03,8]tetradecan-7-one
Clinical data
Trade names Trobicin
AHFS/Drugs.com
Pregnancy
category
  • US: B (No risk in non-human studies)
Legal status
  • not available in US
Identifiers
CAS Registry Number  Y
ATC code J01
PubChem CID:
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  N
ChEMBL  Y
Synonyms (2R,4aR,5aR,6S,7S,8R,9S,9aR,10aS)-4a,7,9-trihydroxy-2-methyl-6,8-bis(methylamino)decahydro-4H-pyrano[2,3-b][1,4]benzodioxin-4-one
Chemical data
Formula C14H24N2O7
Molecular mass 332.35 g/mol
 N   

Spectinomycin, sold under the tradename Trobicin among others, is an health system.[3] The wholesale cost is about 5 USD per dose.[4] It is not available in the United States.[1] It is made from the bacterium Streptomyces spectabilis.[1]

Contents

  • Medical uses 1
  • Side effects 2
  • Mechanism of action 3
  • Biosynthetic mechanism 4
    • Nature 4.1
  • History 5
  • References 6

Medical uses

It is given by injection to treat gonorrhea, especially in patients who are allergic to penicillins.

This antibiotic is no longer available in the United States. A resistance-conferring gene for spectinomycin can also be used as a selection marker in bacteria for molecular cloning purposes. Furthermore, spectinomycin is used as a selection agent for transformed plant cells that contain the selectable marker gene Spcr.[5]

Side effects

Side effects include itching, chills, stomachache, and red rash.

Mechanism of action

Spectinomycin binds to the 30S subunit of the bacterial ribosome and interrupts protein synthesis. One form of resistance has emerged in the 16S ribosomal RNA in Pasteurella multocida.[6]

Biosynthetic mechanism

Proposed spectinomycin biosynthesis

Biosynthesis of spectinomycin begins similar to all aminoglycosides, with the formation of an inositol ring. The difference is the initial modification that forms the inositol ring of spectinomycin. The process begins with a glucose-6-phosphate (1a), which is reduced by NADH to form a ketone at C2 (2a). This ketone is then formed into a primary amine group through PLP and glutamine transamination (3a). This process is repeated again at C4 to form a second primary amine (4a). Once these two amines are present, the glucose ring is ready to be methylated through two S-adenosyl methionine molecules (5a). With this methylation, the glucose ring is finally ready to be converted into an inositol ring through inositol cyclase (6a). This can then be hydrolyzed to get rid of the phosphate group, making the inositol ring necessary for spectinomycin (7a).

While all this happens, an alternate pathway is occurring creating the sugar functional group from a similar starting product. In this pathway, glucose-1-phosphate is used as the starting product (1b). This is converted into a TDP glucose through TDP synthase (2b). TDP glucose then has the hydroxyl removed from C6 through a hydratase enzyme (3b), which is then reduced through NADH at C4 creating a new product (4b). With this ketone present, PLP and glutamine can come in to convert it to a primary amine (5b) which can then be removed through a deaminase (6b). This conversion to 6b is also accompanied by a double reduction at C4 and C3 through two more NADH molecules, giving the final product necessary to form the aminoglycoside. With this, products 7a and 6b can come together, removing the TDP functional group and combining with the sugar molecule to form the aminoglycoside spectinomycin.[7]

Nature

It is in defence mechanism against predators.

History

Spectinomycin was discovered 1961.[2] A disruption in the supply occurred in 2001.[8]

References

  1. ^ a b c d e "Spectinomycin Hydrochloride". The American Society of Health-System Pharmacists. Retrieved Sep 6, 2015. 
  2. ^ a b Textbook of Drug Design and Discovery, Fourth Edition. CRC Press. 2009. p. 438.  
  3. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  4. ^ "Spectinomycin". International Drug Price Indicator Guide. Retrieved 7 September 2015. 
  5. ^ "Spectinomycin Hydrochloride" (pdf). Toku-E. 2010-10-10. Retrieved 2012-06-11. 
  6. ^ Kehrenberg C, Schwarz S (June 2007). "Mutations in 16S rRNA and ribosomal protein S5 associated with high-level spectinomycin resistance in Pasteurella multocida". Antimicrob. Agents Chemother. 51 (6): 2244–6.  
  7. ^ Dewick, Paul M. (4 Feb 2009). Medicinal Natural Products: A Biosynthetic Approach, 3rd Edition. Wiley Online Library: Wiley. pp. 485–508.  
  8. ^ "From the Centers for Disease Control and Prevention. Update on spectinomycin availability in the United States". JAMA 286 (11): 1308–9. September 2001.  
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.