Kanamycin

Kanamycin

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	D
Legal status	?
Routes of administration	Oral, intravenous, intramuscular
Pharmacokinetic data
Bioavailability	very low after oral delivery
Metabolism	Unknown
Half-life	2 hours 30 minutes
Excretion	Urine (as unchanged drug)
Identifiers
CAS Registry Number	59-01-8 Y
ATC code	A07AA08 J01GB04 S01AA24
PubChem	CID 6032
DrugBank	DB01172 Y
ChemSpider	5810 Y
UNII	RUC37XUP2P Y
ChEBI	CHEBI:17630 Y
ChEMBL	CHEMBL1384 Y
PDB ligand ID	KAN (PDBe, RCSB PDB)
Chemical data
Formula	C18H36N4O11
Molecular mass	484.499
SMILES O([C@@H]2[C@@H](O)[C@H](O[C@H]1O[C@H](CN)[C@@H](O)[C@H](O)[C@H]1O)[C@@H](N)C[C@H]2N)[C@H]3O[C@@H]([C@@H](O)[C@H](N)[C@H]3O)CO
InChI InChI=1S/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1  Y Key:SBUJHOSQTJFQJX-NOAMYHISSA-N  Y
Y (what is this?)  (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.

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

^[2]

Mechanism

Kanamycin interacts with the 30S subunit of prokaryotic ribosomes. It induces substantial amounts of mistranslation and indirectly inhibits translocation during protein synthesis.^[3][4]

Composition

Kanamycin is a mixture of three main components: kanamycin A, B, and C. Kanamycin A is the major component in kanamycin.^[5] 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.^[6]

Side effects

Serious side effects include tinnitus or loss of hearing, toxicity to kidneys, and allergic reactions to the drug.^[7]

Use in research: kanamycin resistance

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^[8] 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 (kan^r from transposon Tn903) under control of the strong TEF promoter from Ashbya gossypii.^[9][10]

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.^[9][11]

References

External links

• From kanamycin-evopure.com:
  • Technical Information
  • Purity Survey
  • Toxicity Data
  • Working Concentrations
  • Kanamycin Impurities