Kanamycin
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| Systematic (IUPAC) name | |
|---|---|
|
2-(aminomethyl)- 6-[4,6-diamino-3- [4-amino-3,5-dihydroxy-6-(hydroxymethyl) tetrahydropyran-2-yl]oxy- 2-hydroxy- cyclohexoxy]- tetrahydropyran- 3,4,5-triol | |
| Clinical data | |
| AHFS/Drugs.com | monograph |
| Pregnancy category |
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| Routes of administration | Oral, intravenous, intramuscular |
| Legal status |
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| Pharmacokinetic data | |
| Bioavailability | very low after oral delivery |
| Metabolism | Unknown |
| Biological half-life | 2 hours 30 minutes |
| Excretion | Urine (as unchanged drug) |
| Identifiers | |
| CAS Number |
59-01-8  |
| ATC code | A07AA08 (WHO) J01GB04 S01AA24 |
| PubChem | CID 6032 |
| DrugBank |
DB01172 |
| ChemSpider |
5810 |
| UNII |
RUC37XUP2P |
| ChEBI |
CHEBI:17630 |
| ChEMBL |
CHEMBL1384 |
| PDB ligand ID | KAN (PDBe, RCSB PDB) |
| Chemical data | |
| Formula | C18H36N4O11 |
| Molar mass | 484.499 |
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| (verify) | |
Kanamycin (also known as kanamycin A) is an aminoglycoside bacteriocidal antibiotic, available in oral, intravenous, and intramuscular forms, and used to treat a wide variety of infections. Kanamycin is isolated from the bacterium Streptomyces kanamyceticus[1] and its most commonly used form is kanamycin sulfate.
It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[2]
Medical uses
Spectrum of activity
Kanamycin has been used to treat infections caused by Gram-negative bacteria including E. coli, Proteus spp., Serratia marcescens, and Klebsiella pneumoniae. The following represents MIC susceptibility data for a few medically significant pathogens:
- Escherichia coli - 0.05 μg/ml - >512 μg/ml
- Klebsiella pneumoniae - 7.5 μg/ml - 128 μg/ml
Side effects
Serious side effects include tinnitus or loss of hearing, toxicity to kidneys, and allergic reactions to the drug.[4]
Mechanism
Kanamycin interacts with the 30S subunit of prokaryotic ribosomes. It gives birth to substantial amounts of mistranslation and indirectly inhibits translocation during protein synthesis.[5][6]
Composition
Kanamycin is a mixture of three main components: kanamycin A, B, and C. Kanamycin A is the major component in kanamycin.[7] The effects of these components do not appear to be widely studied as individual compounds when used against prokaryotic and eukaryotic cells.
Biosynthesis
While the main product produced by Streptomyces kanamyceticus is kanamycin A, additional products are also produced, including kanamycin B, kanamycin C, kanamycin D and kanamycin X.
The kanamycin biosynthetic pathway can be divided into two parts. The first part is common to several aminoglycoside antibiotics, such as butirosin and neomycin. In it a unique aminocyclitol, 2-deoxystreptamine, is biosynthesized from D-glucopyranose 6-phosphate in four steps. At this point the kanamycin pathway splits into two branches due to the promiscuity of the next enzyme, which can utilize two different glycosyl donors - UDP-N-acetyl-α-D-glucosamine and UDP-α-D-glucose. One of the branches forms kanamycin C and kanamycin B, while the other branch forms kanamycin D and kanamycin X. However, both kanamycin B and kanamycin D can be converted to kanamycin A, so both branches of the pathway converge at kanamycin A.[8]
Use in research
Kanamycin is used in molecular biology as a selective agent most commonly to isolate bacteria (e.g., E. coli) which have taken up genes (e.g., of plasmids) coupled to a gene coding for kanamycin resistance (primarily Neomycin phosphotransferase II [NPT II/Neo]). Bacteria that have been transformed with a plasmid containing the kanamycin resistance gene are plated on kanamycin (50-100 ug/ml) containing agar plates or are grown in media containing kanamycin (50-100 ug/ml). Only the bacteria that have successfully taken up the kanamycin resistance gene become resistant and will grow under these conditions. As a powder, kanamycin is white to off-white and is soluble in water (50 mg/ml).
At least one such gene, Atwbc19[9] is native to a plant species, of comparatively large size and its coded protein acts in a manner which decreases the possibility of horizontal gene transfer from the plant to bacteria; it may be incapable of giving resistance to bacteria even if gene transfer occurs.
The KanMX marker
The selection marker kanMX is a hybrid gene consisting of a bacterial aminoglycoside phosphotransferase (kanr from transposon Tn903) under control of the strong TEF promoter from Ashbya gossypii.[10][11]
Mammalian cells, yeast, and other eukaryotes acquire resistance to geneticin (= G418, an aminoglycoside antibiotic similar to kanamycin) when transformed with a kanMX marker. In yeast, the kanMX marker avoids the requirement of auxotrophic markers. In addition, the kanMX marker renders E. coli resistant to kanamycin. In shuttle vectors the KanMX cassette is used with an additional bacterial promoter. Several versions of the kanMX cassette are in use, e.g. kanMX1-kanMX6. They primarily differ by additional restriction sites and other small changes around the actual open reading frame.[10][12]
References
- ↑ Garrod, L.P., et al.: "Antibiotic and Chemotherapy", page 131. Churchill Livingstone, 1981
- ↑ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ↑ http://antibiotics.toku-e.com/antimicrobial_744_6.html
- ↑ Consumer Drug Information: Kanamycin, 2 April 2008, retrieved 2008-05-04
- ↑ Pestka, S.: "The Use of Inhibitors in Studies on Protein Synthesis", Methods in Enzymology 30, pp.261-282, 1975
- ↑ Misumi, M. & Tanaka, N.: "Mechanism of Inhibition of Translocation by Kanamycin and Viomycin: A Comparative Study with Fusidic Acid, Biochem.Biophys.Res.Commun. 92, pp.647-654, 1980
- ↑ United States. National Institutes of Health. Kanamycin Compound Summary. PubChem. Web. 21 Aug. 2012.
- ↑ "kanamycin biosynthesis pathway in MetaCyc". MetaCyc.org. Retrieved 30 September 2014.
- ↑ "Horizontal Gene Transfer: Plant vs. Bacterial Genes for Antibiotic Resistance Scenario's—What's the Difference?". Isb.vt.edu. Retrieved 2013-06-24.
- 1 2 Wach, A.; Brachat, A.; Pöhlmann, R.; Philippsen, P. (1994). "New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae". Yeast 10 (13): 1793–1808. doi:10.1002/yea.320101310. PMID 7747518.
- ↑ Steiner, S.; Philippsen, P. (1994). "Sequence and promoter analysis of the highly expressed TEF gene of the filamentous fungus Ashbya gossypii". Molecular & general genetics : MGG 242 (3): 263–271. doi:10.1007/BF00280415. PMID 8107673.
- ↑ Wach, A. (1996). "PCR-synthesis of marker cassettes with long flanking homology regions for gene disruptions in S. Cerevisiae". Yeast 12 (3): 259–265. doi:10.1002/(SICI)1097-0061(19960315)12:3<259::AID-YEA901>3.0.CO;2-C. PMID 8904338.
External links
- From kanamycin-evopure.com:
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