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Wikipedia

Neomycin

February 16, 2024

Neomycin is an aminoglycoside antibiotic that displays bactericidal activity against gram-negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen. It is generally not effective against gram-positive bacilli and anaerobic gram-negative bacilli. Neomycin comes in oral and topical formulations, including creams, ointments, and eyedrops. Neomycin belongs to the aminoglycoside class of antibiotics that contain two or more amino sugars connected by glycosidic bonds.

Neomycin
Clinical data
Trade namesNeo-rx
AHFS/Drugs.comMonograph
MedlinePlusa682274
Routes of
administration		Topical, oral
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNone
Protein bindingN/A
MetabolismN/A
Elimination half-life2 to 3 hours
Identifiers
  • (2RS,3S,4S,5R)-5-Amino-2-(aminomethyl)-6-((2R,3S,4R,5S)-5-((1R,2R,5R,6R)-3,5-diamino-2-((2R,3S,4R,5S)-3-amino-6-(aminomethyl)-4,5-dihydroxytetrahydro-2H-pyran-2-yloxy)-6-hydroxycyclohexyloxy)-4-hydroxy-2-(hydroxymethyl)tetrahydrofuran-3-yloxy)tetrahydro-2H-pyran-3,4-diol
CAS Number
  • 1404-04-2 Y
PubChem CID
  • 8378
IUPHAR/BPS
  • 709
DrugBank
  • DB00994 Y
ChemSpider
  • 8075 Y
UNII
  • I16QD7X297
KEGG
  • D08260 Y
ChEBI
  • CHEBI:7508 Y
ChEMBL
  • ChEMBL449118 N
ECHA InfoCard100.014.333
Chemical and physical data
FormulaC23H46N6O13
Molar mass614.650 g·mol−1
3D model (JSmol)
  • Interactive image
  • O([C@H]3[C@H](O[C@@H]2O[C@H](CO)[C@@H](O[C@H]1O[C@@H](CN)[C@@H](O)[C@H](O)[C@H]1N)[C@H]2O)[C@@H](O)[C@H](N)C[C@@H]3N)[C@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4N)CN
  • InChI=1S/C23H46N6O13/c24-2-7-13(32)15(34)10(28)21(37-7)40-18-6(27)1-5(26)12(31)20(18)42-23-17(36)19(9(4-30)39-23)41-22-11(29)16(35)14(33)8(3-25)38-22/h5-23,30-36H,1-4,24-29H2/t5-,6+,7+,8?,9+,10+,11-,12+,13+,14-,15+,16-,17+,18-,19+,20-,21+,22-,23-/m0/s1 N
  • Key:PGBHMTALBVVCIT-DPNHOFNISA-N N
 NY (what is this?)  (verify)

Neomycin was discovered in 1949 by microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University. Neomycin received approval for medical use in 1952.[1] Rutgers University was granted the patent for neomycin in 1957.[2]

Discovery edit

Neomycin was discovered in 1949 by the microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University. It is produced naturally by the bacterium Streptomyces fradiae.[3] Synthesis requires specific nutrient conditions in either stationary or submerged aerobic conditions. The compound is then isolated and purified from the bacterium.[4]

Medical uses edit

Neomycin is typically applied as a topical preparation, such as Neosporin (neomycin/polymyxin B/bacitracin). The antibiotic can also be administered orally, in which case it is usually combined with other antibiotics. Neomycin is not absorbed from the gastrointestinal tract and has been used as a preventive measure for hepatic encephalopathy and hypercholesterolemia. By killing bacteria in the intestinal tract, Neomycin keeps ammonia levels low and prevents hepatic encephalopathy, especially before gastrointestinal surgery.[citation needed]

Waksman and Lechevalier originally noted that neomycin was active against streptomycin-resistant bacteria as well as Mycobacterium tuberculosis, the causative agent for tuberculosis.[5] Neomycin has also been used to treat small intestinal bacterial overgrowth. Neomycin is not administered via injection, as it is extremely nephrotoxic (damaging to kidney function) even when compared to other aminoglycosides. The exception is when neomycin is included, in small quantities, as a preservative in some vaccines – typically 25 μg per dose.[6]

Spectrum edit

Similar to other aminoglycosides, neomycin has excellent activity against gram-negative bacteria and is partially effective against gram-positive bacteria. It is relatively toxic to humans, with allergic reactions noted as a common adverse reaction (see: hypersensitivity).[7] Physicians sometimes recommend using antibiotic ointments without neomycin, such as Polysporin.[8] The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant gram-negative bacteria.[9]

  • Enterobacter cloacae: >16 μg/ml
  • Escherichia coli: 1 μg/ml
  • Proteus vulgaris: 0.25 μg/ml

Side effects edit

In 2005–06, Neomycin was the fifth-most-prevalent allergen in patch test results (10.0%).[10] It is also a known GABA gamma-Aminobutyric acid antagonist and can be responsible for seizures and psychosis.[11] Like other aminoglycosides, neomycin has been shown to be ototoxic, causing tinnitus, hearing loss, and vestibular problems in a small number of patients. Neomycin affects the cochlea, which is found in the inner ear.[12] Hearing loss is caused by ear hair cell death, which occurs in response to treatment with neomycin.[13] Patients with existing tinnitus or sensorineural hearing loss are advised to speak with a healthcare practitioner about the risks and side effects prior to taking this medication.[citation needed]

Molecular biology edit

Activity edit

Neomycin's antibacterial activity stems from its binding to the 30S subunit of the prokaryotic ribosome, where it inhibits prokaryotic translation of mRNA.[14]

Neomycin also exhibits a high binding affinity for phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid component of cell membranes.[15]

Resistance edit

Neomycin resistance is conferred by either one of two kanamycin kinase genes.[16] Genes conferring neomycin-resistance are commonly included in DNA plasmids used to establish stable mammalian cell lines expressing cloned proteins in culture. Many commercially available protein expression plasmids contain a neo-resistance gene as a selectable marker. Currently, research is being performed to understand if derivatives of neomycin have the same antibiotic effects while still being effective against neomycin-resistant bacteria.[17]

Biosynthetic pathway edit

Neomycin was first isolated from the Streptomyces fradiae and Streptomyces albogriseus in 1949 (NBRC 12773).[18] Neomycin is a mixture of neomycin B (framycetin); and its epimer neomycin C, the latter component accounting for some 5–15% of the mixture. It is a basic compound that is most active with an alkaline reaction.[5] It is also thermostable and soluble in water (while insoluble in organic solvents).[5] Neomycin has good activity against gram-positive and gram-negative bacteria, but is ototoxic. Its use is thus restricted to the oral treatment of intestinal infections.[19]

Neomycin B is composed of four linked moieties: D-neosamine, 2-deoxystreptamine (2-DOS), D-ribose, and L-neosamine.[citation needed]

Neomycin A, also called neamine, contains D-neosamine and 2-deoxystreptamine. Six genes are responsible for neamine biosynthesis: DOIS gene (btrC, neo7); L-glutamine:DOI aminotransferase gene (btrS, neo6); a putative glycosyltransferase gene (btrM, neo8); a putative aminotransferase (similar to glutamate-1-semialdehyde 2,1-aminomutase) gene (btrB, neo18); a putative alcohol dehydrogenase gene (btrE, neo5); and another putative dehydrogenase (similar to chorine dehydrogenase and related flavoproteins) gene (btrQ, neo11).[20] A deacetylase acting to remove the acetyl group on N-acetylglucosamine moieties of aminoglycoside intermediates (Neo16) remains to be clarified (sequence similar to BtrD).[21]

Next is the attachment of the D-ribose via ribosylation of neamine, using 5-phosphoribosyl-1-diphosphate (PRPP) as the ribosyl donor (BtrL, BtrP);[22] glycosyltransferase (potential homologues RibF, LivF, Parf) gene (Neo15).[23]

Neosamine B (L-neosamine B) is most likely biosynthesized in the same manner as the neosamine C (D-niosamine) in neamine biosynthesis, but with an additional epimerization step required to account for the presence of the epimeric neosamine B in neomycin B.[24]

 
Neomycin B

Neomycin B and C are 23-carbon molecules with a four-ring structure. Three of the rings are six-membered, and one is five-membered.[25] Neomycin B and Neomycin C are stereoisomers of each other and differ by only one stereocenter one giving the R conformation and the other giving the S conformation.[26] Neomycin C can undergo enzymatic synthesis from ribostamycin.[27]

Composition edit

Standard grade neomycin is composed of several related compounds including neomycin A (neamine), neomycin B (framycetin), neomycin C, and a few minor compounds found in much lower quantities. Neomycin B is the most active component in neomycin followed by neomycin C and neomycin A. Neomycin A is an inactive degradation product of the C and B isomers.[28] The quantities of these components in neomycin vary from lot-to-lot depending on the manufacturer and manufacturing process.[29]

DNA binding edit

Aminoglycosides such as neomycin are known for their ability to bind to duplex RNA with high affinity.[30] The association constant for neomycin with A-site RNA is in the 109 M−1 range.[31] However, more than 50 years after its discovery, its DNA-binding properties were still unknown. Neomycin has been shown to induce thermal stabilization of triplex DNA, while having little or almost no effect on the B-DNA duplex stabilization.[32] Neomycin was also shown to bind to structures that adopt an A-form structure, triplex DNA being one of them. Neomycin also includes DNA:RNA hybrid triplex formation.[33]

References edit

  1. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 507. ISBN 9783527607495. from the original on 2020-08-01. Retrieved 2020-05-25.
  2. ^ US 2799620, Waksman SA, Lechevalier HA, "Neomycin and process of preparation", issued 18 July 1957, assigned to Rutgers Research and Educational Foundation. 
  3. ^ "The Nobel Prize in Physiology or Medicine 1952". Nobel Foundation. from the original on 2018-06-19. Retrieved 2008-10-29.
  4. ^ "Neomycin". Pharmaceutical Manufacturing Encyclopedia. Vol. 3 (3rd ed.). 2007. pp. 2415–2416.
  5. ^ a b c Waksman SA, Lechevalier HA (March 1949). "Neomycin, a New Antibiotic Active against Streptomycin-Resistant Bacteria, including Tuberculosis Organisms". Science. New York, N.Y. 109 (2830): 305–7. Bibcode:1949Sci...109..305W. doi:10.1126/science.109.2830.305. PMID 17782716.
  6. ^ Heidary N, Cohen DE (September 2005). "Hypersensitivity reactions to vaccine components". Dermatitis. 16 (3): 115–20. doi:10.1097/01206501-200509000-00004. PMID 16242081. S2CID 31248441.
  7. ^ DermNet dermatitis/neomycin-allergy
  8. ^ . DERMAdoctor.com, Inc. Archived from the original on 2009-07-09. Retrieved 2008-10-19.
  9. ^ "Neomycin sulfate, EP Susceptibility and Minimum Inhibitory Concentration (MIC) Data" (PDF). TOKU-E. (PDF) from the original on 2015-12-22. Retrieved 2014-03-31.
  10. ^ Zug KA, Warshaw EM, Fowler JF, Maibach HI, Belsito DL, Pratt MD, et al. (2009). "Patch-test results of the North American Contact Dermatitis Group 2005-2006". Dermatitis. 20 (3): 149–60. doi:10.2310/6620.2009.08097. PMID 19470301. S2CID 24088485.
  11. ^ Lee C, de Silva AJ (March 1979). "Interaction of neuromuscular blocking effects of neomycin and polymyxin B". Anesthesiology. 50 (3): 218–20. doi:10.1097/00000542-197903000-00010. PMID 219730. S2CID 13551808.
  12. ^ Langman, A. Neomycin ototoxicity. Otolaryngology Head and Neck Surgery 1994, 110, 441-444.
  13. ^ Langman, A. Neomycin ototoxicity. Otolaryngology Head and Neck Surgery 1994, 110, 441-444.
  14. ^ Mehta R, Champney WS (September 2003). "Neomycin and paromomycin inhibit 30S ribosomal subunit assembly in Staphylococcus aureus". Current Microbiology. 47 (3): 237–43. doi:10.1007/s00284-002-3945-9. PMID 14570276. S2CID 23170091.
  15. ^ Gabev E, Kasianowicz J, Abbott T, McLaughlin S (February 1989). "Binding of neomycin to phosphatidylinositol 4,5-bisphosphate (PIP2)". Biochimica et Biophysica Acta (BBA) - Biomembranes. 979 (1): 105–12. doi:10.1016/0005-2736(89)90529-4. PMID 2537103.
  16. ^ "G418/neomycin-cross resistance?". from the original on 2009-06-25. Retrieved 2008-10-19.
  17. ^ Bera, S.; Zhanel, G.; Schweizer, F. Design, Synthesis, and Antibacterial Activities of Neomycin−Lipid Conjugates: Polycationic Lipids with Potent Gram-Positive Activity | Journal of Medicinal Chemistry. Journal of Medicinal Chemistry 2003, 51, 6160-6164.
  18. ^ Waksman SA, Lechevalier HA, Harris DA (September 1949). "Neomycin—Production and Antibiotic Properties 123". The Journal of Clinical Investigation. 28 (5 Pt 1): 934–9. doi:10.1172/JCI102182. PMC 438928. PMID 16695766.
  19. ^ Dewick M (March 2009). Medicinal natural products: a biosynthetic approach (3rd ed.). The Atrium, Southern Gate, Chichester, West Sussex, United Kingdom: John Wiley and Sons Ltd. pp. 508, 510, 511. ISBN 978-0-470-74168-9.
  20. ^ Kudo F, Yamamoto Y, Yokoyama K, Eguchi T, Kakinuma K (December 2005). "Biosynthesis of 2-deoxystreptamine by three crucial enzymes in Streptomyces fradiae NBRC 12773". The Journal of Antibiotics. 58 (12): 766–74. doi:10.1038/ja.2005.104. PMID 16506694.
  21. ^ Park JW, Park SR, Nepal KK, Han AR, Ban YH, Yoo YJ, et al. (October 2011). "Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation". Nature Chemical Biology. 7 (11): 843–52. doi:10.1038/nchembio.671. PMID 21983602.
  22. ^ Kudo F, Fujii T, Kinoshita S, Eguchi T (July 2007). "Unique O-ribosylation in the biosynthesis of butirosin". Bioorganic & Medicinal Chemistry. 15 (13): 4360–8. doi:10.1016/j.bmc.2007.04.040. PMID 17482823.
  23. ^ Fan Q, Huang F, Leadlay PF, Spencer JB (September 2008). "The neomycin biosynthetic gene cluster of Streptomyces fradiae NCIMB 8233: genetic and biochemical evidence for the roles of two glycosyltransferases and a deacetylase". Organic & Biomolecular Chemistry. 6 (18): 3306–14. doi:10.1039/B808734B. PMID 18802637. S2CID 29942953.
  24. ^ Llewellyn NM, Spencer JB (December 2006). "Biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics". Natural Product Reports. 23 (6): 864–74. doi:10.1039/B604709M. PMID 17119636.
  25. ^ National Center for Biotechnology Information Neomycin. https://pubchem.ncbi.nlm.nih.gov/compound/8378 (accessed Nov 5, 2023).
  26. ^ National Center for Biotechnology Information Neomycin. https://pubchem.ncbi.nlm.nih.gov/compound/8378 (accessed Nov 5, 2023).
  27. ^ Kudo F, Kawashima T, Yokoyama K, Eguchi T (November 2009). "Enzymatic preparation of neomycin C from ribostamycin". The Journal of Antibiotics. 62 (11): 643–6. doi:10.1038/ja.2009.88. PMID 19713992.
  28. ^ Cammack R, Attwood TK, Campbell PN, Parish JH, Smith AD, Stirling JL, Vella F (2006). "neomycin". Oxford Dictionary of Biochemistry and Molecular Biology (2nd ed.). Oxford University Press. p. 453.
  29. ^ Tsuji K, Robertson JH, Baas R, McInnis DJ (September 1969). "Comparative study of responses to neomycins B and C by microbiological and gas-liquid chromatographic assay methods". Applied Microbiology. 18 (3): 396–8. doi:10.1128/AEM.18.3.396-398.1969. PMC 377991. PMID 4907002.
  30. ^ Jin Y, Watkins D, Degtyareva NN, Green KD, Spano MN, Garneau-Tsodikova S, Arya DP (January 2016). "Arginine-linked neomycin B dimers: synthesis, rRNA binding, and resistance enzyme activity". MedChemComm. 7 (1): 164–169. doi:10.1039/C5MD00427F. PMC 4722958. PMID 26811742.
  31. ^ Kaul M, Pilch DS (June 2002). "Thermodynamics of aminoglycoside-rRNA recognition: the binding of neomycin-class aminoglycosides to the A site of 16S rRNA". Biochemistry. 41 (24): 7695–706. doi:10.1021/bi020130f. PMID 12056901.
  32. ^ Arya DP, Coffee RL (September 2000). "DNA triple helix stabilization by aminoglycoside antibiotics". Bioorganic & Medicinal Chemistry Letters. 10 (17): 1897–9. doi:10.1016/S0960-894X(00)00372-3. PMID 10987412.
  33. ^ Arya DP, Coffee RL, Charles I (November 2001). "Neomycin-induced hybrid triplex formation". Journal of the American Chemical Society. 123 (44): 11093–4. doi:10.1021/ja016481j. PMID 11686727.

February 16, 2024
neomycin, aminoglycoside, antibiotic, that, displays, bactericidal, activity, against, gram, negative, aerobic, bacilli, some, anaerobic, bacilli, where, resistance, arisen, generally, effective, against, gram, positive, bacilli, anaerobic, gram, negative, bac. Neomycin is an aminoglycoside antibiotic that displays bactericidal activity against gram negative aerobic bacilli and some anaerobic bacilli where resistance has not yet arisen It is generally not effective against gram positive bacilli and anaerobic gram negative bacilli Neomycin comes in oral and topical formulations including creams ointments and eyedrops Neomycin belongs to the aminoglycoside class of antibiotics that contain two or more amino sugars connected by glycosidic bonds NeomycinClinical dataTrade namesNeo rxAHFS Drugs comMonographMedlinePlusa682274Routes ofadministrationTopical oralATC codeA01AB08 WHO A07AA01 WHO B05CA09 WHO D06AX04 WHO J01GB05 WHO R02AB01 WHO S01AA03 WHO S02AA07 WHO S03AA01 WHO Legal statusLegal statusUS only but OTC in Neosporin and similar ointmentsPharmacokinetic dataBioavailabilityNoneProtein bindingN AMetabolismN AElimination half life2 to 3 hoursIdentifiersIUPAC name 2RS 3S 4S 5R 5 Amino 2 aminomethyl 6 2R 3S 4R 5S 5 1R 2R 5R 6R 3 5 diamino 2 2R 3S 4R 5S 3 amino 6 aminomethyl 4 5 dihydroxytetrahydro 2H pyran 2 yloxy 6 hydroxycyclohexyloxy 4 hydroxy 2 hydroxymethyl tetrahydrofuran 3 yloxy tetrahydro 2H pyran 3 4 diolCAS Number1404 04 2 YPubChem CID8378IUPHAR BPS709DrugBankDB00994 YChemSpider8075 YUNIII16QD7X297KEGGD08260 YChEBICHEBI 7508 YChEMBLChEMBL449118 NECHA InfoCard100 014 333Chemical and physical dataFormulaC 23H 46N 6O 13Molar mass614 650 g mol 13D model JSmol Interactive imageSMILES O C H 3 C H O C H 2O C H CO C H O C H 1O C H CN C H O C H O C H 1N C H 2O C H O C H N C C H 3N C H 4O C H C H O C H O C H 4N CNInChI InChI 1S C23H46N6O13 c24 2 7 13 32 15 34 10 28 21 37 7 40 18 6 27 1 5 26 12 31 20 18 42 23 17 36 19 9 4 30 39 23 41 22 11 29 16 35 14 33 8 3 25 38 22 h5 23 30 36H 1 4 24 29H2 t5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 m0 s1 NKey PGBHMTALBVVCIT DPNHOFNISA N N N Y what is this verify Neomycin was discovered in 1949 by microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University Neomycin received approval for medical use in 1952 1 Rutgers University was granted the patent for neomycin in 1957 2 Contents 1 Discovery 2 Medical uses 2 1 Spectrum 3 Side effects 4 Molecular biology 4 1 Activity 4 2 Resistance 5 Biosynthetic pathway 6 Composition 7 DNA binding 8 ReferencesDiscovery editNeomycin was discovered in 1949 by the microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University It is produced naturally by the bacterium Streptomyces fradiae 3 Synthesis requires specific nutrient conditions in either stationary or submerged aerobic conditions The compound is then isolated and purified from the bacterium 4 Medical uses editNeomycin is typically applied as a topical preparation such as Neosporin neomycin polymyxin B bacitracin The antibiotic can also be administered orally in which case it is usually combined with other antibiotics Neomycin is not absorbed from the gastrointestinal tract and has been used as a preventive measure for hepatic encephalopathy and hypercholesterolemia By killing bacteria in the intestinal tract Neomycin keeps ammonia levels low and prevents hepatic encephalopathy especially before gastrointestinal surgery citation needed Waksman and Lechevalier originally noted that neomycin was active against streptomycin resistant bacteria as well as Mycobacterium tuberculosis the causative agent for tuberculosis 5 Neomycin has also been used to treat small intestinal bacterial overgrowth Neomycin is not administered via injection as it is extremely nephrotoxic damaging to kidney function even when compared to other aminoglycosides The exception is when neomycin is included in small quantities as a preservative in some vaccines typically 25 mg per dose 6 Spectrum edit Similar to other aminoglycosides neomycin has excellent activity against gram negative bacteria and is partially effective against gram positive bacteria It is relatively toxic to humans with allergic reactions noted as a common adverse reaction see hypersensitivity 7 Physicians sometimes recommend using antibiotic ointments without neomycin such as Polysporin 8 The following represents minimum inhibitory concentration MIC susceptibility data for a few medically significant gram negative bacteria 9 Enterobacter cloacae gt 16 mg ml Escherichia coli 1 mg ml Proteus vulgaris 0 25 mg mlSide effects editIn 2005 06 Neomycin was the fifth most prevalent allergen in patch test results 10 0 10 It is also a known GABA gamma Aminobutyric acid antagonist and can be responsible for seizures and psychosis 11 Like other aminoglycosides neomycin has been shown to be ototoxic causing tinnitus hearing loss and vestibular problems in a small number of patients Neomycin affects the cochlea which is found in the inner ear 12 Hearing loss is caused by ear hair cell death which occurs in response to treatment with neomycin 13 Patients with existing tinnitus or sensorineural hearing loss are advised to speak with a healthcare practitioner about the risks and side effects prior to taking this medication citation needed Molecular biology editActivity edit Neomycin s antibacterial activity stems from its binding to the 30S subunit of the prokaryotic ribosome where it inhibits prokaryotic translation of mRNA 14 Neomycin also exhibits a high binding affinity for phosphatidylinositol 4 5 bisphosphate PIP2 a phospholipid component of cell membranes 15 Resistance edit Neomycin resistance is conferred by either one of two kanamycin kinase genes 16 Genes conferring neomycin resistance are commonly included in DNA plasmids used to establish stable mammalian cell lines expressing cloned proteins in culture Many commercially available protein expression plasmids contain a neo resistance gene as a selectable marker Currently research is being performed to understand if derivatives of neomycin have the same antibiotic effects while still being effective against neomycin resistant bacteria 17 Biosynthetic pathway editNeomycin was first isolated from the Streptomyces fradiae and Streptomyces albogriseus in 1949 NBRC 12773 18 Neomycin is a mixture of neomycin B framycetin and its epimer neomycin C the latter component accounting for some 5 15 of the mixture It is a basic compound that is most active with an alkaline reaction 5 It is also thermostable and soluble in water while insoluble in organic solvents 5 Neomycin has good activity against gram positive and gram negative bacteria but is ototoxic Its use is thus restricted to the oral treatment of intestinal infections 19 Neomycin B is composed of four linked moieties D neosamine 2 deoxystreptamine 2 DOS D ribose and L neosamine citation needed Neomycin A also called neamine contains D neosamine and 2 deoxystreptamine Six genes are responsible for neamine biosynthesis DOIS gene btrC neo7 L glutamine DOI aminotransferase gene btrS neo6 a putative glycosyltransferase gene btrM neo8 a putative aminotransferase similar to glutamate 1 semialdehyde 2 1 aminomutase gene btrB neo18 a putative alcohol dehydrogenase gene btrE neo5 and another putative dehydrogenase similar to chorine dehydrogenase and related flavoproteins gene btrQ neo11 20 A deacetylase acting to remove the acetyl group on N acetylglucosamine moieties of aminoglycoside intermediates Neo16 remains to be clarified sequence similar to BtrD 21 Next is the attachment of the D ribose via ribosylation of neamine using 5 phosphoribosyl 1 diphosphate PRPP as the ribosyl donor BtrL BtrP 22 glycosyltransferase potential homologues RibF LivF Parf gene Neo15 23 Neosamine B L neosamine B is most likely biosynthesized in the same manner as the neosamine C D niosamine in neamine biosynthesis but with an additional epimerization step required to account for the presence of the epimeric neosamine B in neomycin B 24 nbsp Neomycin BNeomycin B and C are 23 carbon molecules with a four ring structure Three of the rings are six membered and one is five membered 25 Neomycin B and Neomycin C are stereoisomers of each other and differ by only one stereocenter one giving the R conformation and the other giving the S conformation 26 Neomycin C can undergo enzymatic synthesis from ribostamycin 27 Composition editStandard grade neomycin is composed of several related compounds including neomycin A neamine neomycin B framycetin neomycin C and a few minor compounds found in much lower quantities Neomycin B is the most active component in neomycin followed by neomycin C and neomycin A Neomycin A is an inactive degradation product of the C and B isomers 28 The quantities of these components in neomycin vary from lot to lot depending on the manufacturer and manufacturing process 29 DNA binding editAminoglycosides such as neomycin are known for their ability to bind to duplex RNA with high affinity 30 The association constant for neomycin with A site RNA is in the 109 M 1 range 31 However more than 50 years after its discovery its DNA binding properties were still unknown Neomycin has been shown to induce thermal stabilization of triplex DNA while having little or almost no effect on the B DNA duplex stabilization 32 Neomycin was also shown to bind to structures that adopt an A form structure triplex DNA being one of them Neomycin also includes DNA RNA hybrid triplex formation 33 References edit Fischer J Ganellin CR 2006 Analogue based Drug Discovery John Wiley amp Sons p 507 ISBN 9783527607495 Archived from the original on 2020 08 01 Retrieved 2020 05 25 US 2799620 Waksman SA Lechevalier HA Neomycin and process of preparation issued 18 July 1957 assigned to Rutgers Research and Educational Foundation The Nobel Prize in Physiology or Medicine 1952 Nobel Foundation Archived from the original on 2018 06 19 Retrieved 2008 10 29 Neomycin Pharmaceutical Manufacturing Encyclopedia Vol 3 3rd ed 2007 pp 2415 2416 a b c Waksman SA Lechevalier HA March 1949 Neomycin a New Antibiotic Active against Streptomycin Resistant Bacteria including Tuberculosis Organisms Science New York N Y 109 2830 305 7 Bibcode 1949Sci 109 305W doi 10 1126 science 109 2830 305 PMID 17782716 Heidary N Cohen DE September 2005 Hypersensitivity reactions to vaccine components Dermatitis 16 3 115 20 doi 10 1097 01206501 200509000 00004 PMID 16242081 S2CID 31248441 DermNet dermatitis neomycin allergy Your Medicine Cabinet DERMAdoctor com Inc Archived from the original on 2009 07 09 Retrieved 2008 10 19 Neomycin sulfate EP Susceptibility and Minimum Inhibitory Concentration MIC Data PDF TOKU E Archived PDF from the original on 2015 12 22 Retrieved 2014 03 31 Zug KA Warshaw EM Fowler JF Maibach HI Belsito DL Pratt MD et al 2009 Patch test results of the North American Contact Dermatitis Group 2005 2006 Dermatitis 20 3 149 60 doi 10 2310 6620 2009 08097 PMID 19470301 S2CID 24088485 Lee C de Silva AJ March 1979 Interaction of neuromuscular blocking effects of neomycin and polymyxin B Anesthesiology 50 3 218 20 doi 10 1097 00000542 197903000 00010 PMID 219730 S2CID 13551808 Langman A Neomycin ototoxicity Otolaryngology Head and Neck Surgery 1994 110 441 444 Langman A Neomycin ototoxicity Otolaryngology Head and Neck Surgery 1994 110 441 444 Mehta R Champney WS September 2003 Neomycin and paromomycin inhibit 30S ribosomal subunit assembly in Staphylococcus aureus Current Microbiology 47 3 237 43 doi 10 1007 s00284 002 3945 9 PMID 14570276 S2CID 23170091 Gabev E Kasianowicz J Abbott T McLaughlin S February 1989 Binding of neomycin to phosphatidylinositol 4 5 bisphosphate PIP2 Biochimica et Biophysica Acta BBA Biomembranes 979 1 105 12 doi 10 1016 0005 2736 89 90529 4 PMID 2537103 G418 neomycin cross resistance Archived from the original on 2009 06 25 Retrieved 2008 10 19 Bera S Zhanel G Schweizer F Design Synthesis and Antibacterial Activities of Neomycin Lipid Conjugates Polycationic Lipids with Potent Gram Positive Activity Journal of Medicinal Chemistry Journal of Medicinal Chemistry 2003 51 6160 6164 Waksman SA Lechevalier HA Harris DA September 1949 Neomycin Production and Antibiotic Properties 123 The Journal of Clinical Investigation 28 5 Pt 1 934 9 doi 10 1172 JCI102182 PMC 438928 PMID 16695766 Dewick M March 2009 Medicinal natural products a biosynthetic approach 3rd ed The Atrium Southern Gate Chichester West Sussex United Kingdom John Wiley and Sons Ltd pp 508 510 511 ISBN 978 0 470 74168 9 Kudo F Yamamoto Y Yokoyama K Eguchi T Kakinuma K December 2005 Biosynthesis of 2 deoxystreptamine by three crucial enzymes in Streptomyces fradiae NBRC 12773 The Journal of Antibiotics 58 12 766 74 doi 10 1038 ja 2005 104 PMID 16506694 Park JW Park SR Nepal KK Han AR Ban YH Yoo YJ et al October 2011 Discovery of parallel pathways of kanamycin biosynthesis allows antibiotic manipulation Nature Chemical Biology 7 11 843 52 doi 10 1038 nchembio 671 PMID 21983602 Kudo F Fujii T Kinoshita S Eguchi T July 2007 Unique O ribosylation in the biosynthesis of butirosin Bioorganic amp Medicinal Chemistry 15 13 4360 8 doi 10 1016 j bmc 2007 04 040 PMID 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