Aminoglycoside Interactions with RNAs and Nucleases

  • L.A. Kirsebom
  • A. Virtanen
  • N.E. Mikkelsen
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 173)


One of the major challenges in medicine today is the development of new antibiotics as well as effective antiviral agents. The well-known aminoglycosides interact and interfere with the function of several noncoding RNAs, among which ribosomal RNAs (rRNAs) are the best studied. Aminoglycosides are also known to interact with proteins such as ribonucleases. Here we review our current understanding of the interaction between aminoglycosides and RNA. Moreover, we discuss briefly mechanisms behind the inactivation of aminoglycosides, a major concern due to the increasing appearance of multiresistant bacterial strains. Taken together, the general knowledge about aminoglycoside and RNA interaction is of utmost importance in the process of identifying/developing the next generation or new classes of antibiotics. In this perspective, previously unrecognized as well as known noncoding RNAs, apart from rRNA, are promising targets to explore.


RNA Aminoglycosides Metal ions Small ligands Antibiotics 


  1. Agnelli F, Sucheck SJ, Marby KA, Rabuka D, Yao S-L, Sears PS, Liang F-S, Wong C-H (2004) Dimeric aminoglycosides as antibiotics. Angew Chem Int Ed Engl 43:1562–1566CrossRefPubMedGoogle Scholar
  2. Altman S, Kirsebom LA (1999) Ribonuclease P. In: Gesteland R, Cech T, Atkins J (eds) RNA world II. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, pp 351–380Google Scholar
  3. Ambrose V (2001) MicroRNAs: tiny regulators with great potential (minireview). Cell 107:823–826Google Scholar
  4. Archibald S, Duong M (1984) Manganese acquisition by Lactobacillus plantarum. J Bacteriol 158:1–6PubMedGoogle Scholar
  5. Ban N, Nissen P, Hansen J, Moore PB, Steitz TA (2000) The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science 289:905–920CrossRefPubMedGoogle Scholar
  6. Begg EJ, Barclay ML (1995) Aminoglycosides—50 years on. Br J Clin Pharmacol 39:597–603PubMedGoogle Scholar
  7. Berridge MJ, Bootman MD, Lipp P (1998) Calcium—a life and death signal. Nature 395:645–648CrossRefPubMedGoogle Scholar
  8. Brännvall M, Kirsebom LA (2001) Metal ion cooperativity in ribozyme cleavage of RNA. Proc Natl Acad Sci USA 98:12943–12947PubMedGoogle Scholar
  9. Brännvall M, Mikkelesen NE, Kirsebom LA (2001) Monitoring the structure of Escherichia coli RNase P RNA in the presence of various metal ion. Nucleic Acids Res 29:1426–1432PubMedGoogle Scholar
  10. Brännvall M, Kikovska E, Kirsebom LA (2004) Cross talk in RNase P RNA mediated cleavage. Nucleic Acids Res 32:5418–5429PubMedGoogle Scholar
  11. Brodersen DE, Clemons WM Jr, Carter AP, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V (2000) The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell 103:1143–1154CrossRefPubMedGoogle Scholar
  12. Brown RS, Hingerty BE, Dewan JC, Klug A (1983) Pb(II)-catalysed cleavage of the sugar-phosphate backbone of yeast tRNAPhe—implications for lead toxicity and self-splicing RNA. Nature 303:543–546CrossRefPubMedGoogle Scholar
  13. Brown RS, Dewan JC, Klug A (1985) Crystallographic and biochemical investigation of the lead(II)-catalyzed hydrolysis of yeast phenylalanine tRNA. Biochemistry 24:4785–4801PubMedGoogle Scholar
  14. Carter AP, Clemons WM, Brodersen DE, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V (2000) Functional insights from the structure of the 30S ribosomal subunit and its interaction with antibiotics. Nature 407:340–348PubMedGoogle Scholar
  15. Cheng AC, Calabro V, Frankel AD (2001) Design of RNA-binding proteins and ligands. Curr Opin Struct Biol 11:478–484CrossRefPubMedGoogle Scholar
  16. Chia JS, Wu HL, Wang HW, Chen DS, Chen PJ (1997) Inhibition of hepatitis delta virus genomic ribozyme self-cleavage by aminoglycosides. J Biomed Sci 4:208–216CrossRefPubMedGoogle Scholar
  17. Corvaisier S, Bordeau V, Felden B (2002) Inhibition of transfer messenger RNA aminoacylation and trans-translation by aminoglycoside antibiotics. J Biol Chem 278:14788–14797Google Scholar
  18. Davies J (1994) New pathogens and old resistance genes. Microbiologica 10:9–12Google Scholar
  19. Davies J, Wright GD (1997) Bacterial resistance to aminoglycoside antibiotics. Trends Microbiol 5:234–240CrossRefPubMedGoogle Scholar
  20. Davies J, von Ahsen U, Schroeder R (1993) Antibiotics and the RNA world: a role for low-molecular-weight effectors in biochemical evolution? In: Gesteland RF, Atkins JF (eds) The RNA world. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 185–204Google Scholar
  21. DeLano WL (2002) The PyMOL molecular graphics system on the World Wide Web: Cited 10 June 2005Google Scholar
  22. Dessen A, Di Guilmi AM, Vernet T, Dideberg O (2001) Molecular mechanisms of antibiotic resistance in gram-positive pathogens. Curr Drug Targets Infect Disord 1:63–77CrossRefPubMedGoogle Scholar
  23. Earnshaw DJ, Gait MJ (1998) Hairpin ribozyme cleavage catalysed by aminoglycoside antibiotics and the polyamine spermine in the absence of metal ions. Nucleic Acids Res 26:5551–5561CrossRefPubMedGoogle Scholar
  24. Eubank TD, Biswas R, Jovanovic M, Litovchick A, Lapidot A, Gopalan V (2002) Inhibition of bacterial RNase P by aminoglycoside-arginine conjugates. FEBS Lett 511:107–112CrossRefPubMedGoogle Scholar
  25. Faber C, Sticht H, Schweimer K, Rösch P (2000) Structural rearrangements of HIV-1 Tatresponsive RNA upon binding of neomycin B. J Biol Chem 275:20660–20666CrossRefPubMedGoogle Scholar
  26. Fang XW, Yang XJ, Littrell K, Niranjanakumari S, Thiyagarajan P, Fierke CA, Sosnick TR, Pan T (2001) The Bacillus subtilis RNase P holoenzyme contains two RNase P RNA and two RNase P protein subunits. RNA 7:233–241CrossRefPubMedGoogle Scholar
  27. Fourmy D, Recht MI, Blanchard SC, Puglisi JD (1996) Structure of the A site of E. coli 16 S rRNA complexed with an aminoglycoside antibiotic. Science 274:1367–1371CrossRefPubMedGoogle Scholar
  28. Fourmy D, Recht MI, Puglisi JD (1998a) Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 S rRNA. J Mol Biol 277:347–362PubMedGoogle Scholar
  29. Fourmy D, Yoshizawa S, Puglisi JD (1998b) Paromomycin binding induces a local conformational change in the A-site of 16 S rRNA. J Mol Biol 277:333–345PubMedGoogle Scholar
  30. Gegenheimer P, Apirion D (1981) Processing of prokaryotic ribonucleic acid. Microbiol Rev 45:502–541PubMedGoogle Scholar
  31. Giegé R, Sissler M, Florentz C (1998) Universal rules and idiosyncratic features in tRNA identity. Nucleic Acids Res 26:5017–5035PubMedGoogle Scholar
  32. Gottesman S (2004) The small RNA regulators of Escherichia coli: Roles and mechanisms. Annu Rev Microbiol 58:303–338CrossRefPubMedGoogle Scholar
  33. Griffey RH, Hofstadler SA, Sannes-Lowery KA, Ecker DJ, Crooke ST (1999) Determinants of aminoglycoside-binding specificity for rRNA by using mass spectrometry. Proc Natl Acad Sci USA 96:10129–10133CrossRefPubMedGoogle Scholar
  34. Grundy FJ, Henkin TM (2004) Regulation of gene expression by effectors that bind to RNA. Curr Opin Microbiol 7:126–131CrossRefPubMedGoogle Scholar
  35. Guerrier-Takada C, Gardiner K, Marsh T, Pace N, Altman S (1983) The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35:849–857PubMedGoogle Scholar
  36. Hermann T (2003) Chemical and functional diversity of small molecule ligands for RNA. Biopolymers 70:4–18CrossRefPubMedGoogle Scholar
  37. Hermann T, Patel DJ (2000) Adaptive recognition by nucleic acid aptamers. Science 287:820–825CrossRefPubMedGoogle Scholar
  38. Hermann T, Westhof E (1998) Aminoglycoside binding to the hammerhead ribozyme: a general model for the interaction of cationic antibiotics with RNA. J Mol Biol 276:903–912CrossRefPubMedGoogle Scholar
  39. Hermann T, Westhof E (1999) Docking of cationic antibiotics to negatively charged pockets in RNA folds. J Med Chem 42:1250–1251CrossRefPubMedGoogle Scholar
  40. Hershberg R, Altuvia S, Margalit H (2003) A survey of small RNA-encoding genes in Escherichia coli. Nucleic Acids Res 31:1813–1820CrossRefPubMedGoogle Scholar
  41. Hertweck M, Hiller R, Mueller MW (2002) Inhibition of nuclear pre-mRNA splicing by antibiotics in vitro. Eur J Biochem 269:175–183CrossRefPubMedGoogle Scholar
  42. Hsu M, Berg P (1978) Altering the specificity of restriction endonuclease: effect of replacing Mg2+ with Mn2+. Biochemistry 17:131–138CrossRefPubMedGoogle Scholar
  43. Huang C, Wolfgang MC, Withey J, Kommey M, Friedman DI (2000) Charged tmRNA but not tmRNA-mediated proteolysis is essential for Neisseria gonorrhoeae viability. EMBO J 19:1098–1107PubMedGoogle Scholar
  44. Hutchin T, Cortopassi G (1994) Proposed molecular and cellular mechanism for aminoglycoside ototoxicity. Antimicrob Agents Chemother 38:2517–2520PubMedGoogle Scholar
  45. Hyun Ryu D, Rando RR (2001) Aminoglycoside binding to human and bacterialA-site rRNA decoding region constructs. Bioorg Med Chem 9:2601–2608Google Scholar
  46. Ikemura T, Dahlberg JE (1973) Small ribonucleic acids of Escherichia coli. II. Noncoordinate accumulation during stringent control. J Biol Chem 258:5033–5041Google Scholar
  47. Jovine L (2003) Nuccyl 10 June 2005Google Scholar
  48. Jovine L, Djordjevic S, Rhodes D (2000) The crystal structure of yeast phenylalanine tRNA at 2.0 Å resolution: cleavage by Mg2+ in 15-year-old crystals. J Mol Biol 301:401–414CrossRefPubMedGoogle Scholar
  49. Keiler KC, Waller PR, Sauer RT (1996) Role of tagging system in degradation of proteins synthesized from damaged messenger RNA. Science 271:990–993PubMedGoogle Scholar
  50. Kirsebom LA, Virtanen A (2001) Inhibition of RNase P processing. In: Schroeder R, Wallis MG (eds) RNA-binding antibiotics. Molecular Biology Intelligence Unit 13,, Austin. Landes Biosciences, Georgetown, pp 56–72Google Scholar
  51. Kotra LP, Haddad J, Mobashery S (2000) Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob Agents Chemother 44:3249–3256CrossRefPubMedGoogle Scholar
  52. Kovrigina E, Wesolowski D, Altman S (2003) Coordinate inhibition of expression of several genes for protein subunits of human nuclear RNase P. Proc Natl Acad Sci USA 100:1598–1602CrossRefPubMedGoogle Scholar
  53. Labuda D, Striker G, Porschke D (1984) Mechanism of codon recognition by transfer RNA and codon-induced tRNA association. J Mol Biol 174:587–604CrossRefPubMedGoogle Scholar
  54. Lazarus and Kitron (1973) Neomycin inhibition of DNA polymerase. Biochem Pharmacol 22:3115–3117CrossRefPubMedGoogle Scholar
  55. Litovchick A, Lapidot A, Eisenstein M, Kalinkovich A, Borkow G (2001) Neomycin B-arginine conjugate, a novel HIV-1 Tat antagonist: synthesis and anti-HIV activities. Biochemistry 40:15612–15623CrossRefPubMedGoogle Scholar
  56. Luedtke NW, Liu Q, Tor Y (2003) RNA-ligand interactions: affinity and specificity of aminoglycoside dimmers and acridine conjugates to the HIV-1 rev response element. Biochemistry 42:11391–11403CrossRefPubMedGoogle Scholar
  57. Mandal M, Boese B, Barrick JE, Winkler WC, Breaker RR (2003) Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 113:577–586CrossRefPubMedGoogle Scholar
  58. Mattick JS (2003) Challenging the dogma: the hidden layer of non-protein-coding RNAs in complex organisms. Bioessays 25:930–939CrossRefPubMedGoogle Scholar
  59. McDonald LJ, Mamrack MD (1995) Phosphoinositide hydrolysis by phospholipase C modulated by multivalent cations La(3+), Al(3+), neomycin, polyamines, and melittin. J Lipid Mediat Cell Signal 11:81–91CrossRefPubMedGoogle Scholar
  60. McManus MT (2004) Small RNAs and immunity. Immunity 21:747–756CrossRefPubMedGoogle Scholar
  61. Mei H-Y, Galan AA, Halim NS, Mack DP, Moreland DW, Sanders KB, Truong HN, Czarnik AW (1995) Inhibition of an HIV-1 Tat-derived peptide binding to TAR RNA by aminoglycoside antibiotics. Bioorg Med Chem Lett 5:2755–2760CrossRefGoogle Scholar
  62. Mikkelsen NE, Brännvall M, Virtanen A, Kirsebom LA (1999) Inhibition of RNase P RNA cleavage by aminoglycosides. Proc Natl Acad Sci USA 96:6155–6160CrossRefPubMedGoogle Scholar
  63. Mikkelsen NE, Johansson K, Virtanen A, Kirsebom LA (2001) Aminoglycoside binding displaces a divalent metal ion in a tRNA-neomycin B complex. Nat Struct Biol 8:510–514CrossRefPubMedGoogle Scholar
  64. Mingeot-Leclercq MP, Tulkens PM (1999) Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 43:1003–1012PubMedGoogle Scholar
  65. Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM (1999) Aminoglycosides: activity and resistance. Antimicrob Agents Chemother 43:727–737PubMedGoogle Scholar
  66. Møller T, Franch T, Udesen C, Gerdes K, Valentin-Hansen P (2002) Spot 42 RNA mediates discoordinate expression of the E. coli galactose operon. Genes Dev 16:1696–1706PubMedGoogle Scholar
  67. Nahvi A, Sudarsan N, Ebert MS, Zou X, Brown KL, Breaker RR (2002) Genetic control by a metabolite binding mRNA. Chem Biol 9:1043–1049CrossRefPubMedGoogle Scholar
  68. Nissen P, Hansen J, Ban N, Moore PB, Steitz TA (2000) The structural basis of ribosome activity in peptide bond synthesis. Science 289:920–930CrossRefPubMedGoogle Scholar
  69. Ogle JM, Brodersen DE, Clemons Jr WM, Tarry MJ, Carter AP, Ramakrishnan V (2001) Crystal structure of an initiation factor bound to the 30S ribosomal subunit. Science 292:897–902CrossRefPubMedGoogle Scholar
  70. Patel DJ, Suri AK, Jiang F, Jiang L, Fan P, Kumar RA, Nonin S (1997) Structure, recognition and adaptive binding in RNA aptamer complexes. J Mol Biol 272:645–664CrossRefPubMedGoogle Scholar
  71. Pedersen LC, Benning MM, Holden HM (1995) Structural investigation of the antibiotic and ATP-binding sites in kanamycin nucleotidyltransferase. Biochemistry 34:13305–13311PubMedGoogle Scholar
  72. Piolleti M, Schlünzen F, Harms J, Zarivach R, Glühmann M, Avila H, Bashan A, Bartels H, Auerbach T, Jacobi C, Hartsch T, Yonath A, Franceschi F (2001) Crystal structures of complexes of the small ribosomal subunits with tetracycline, edeine and IF3. EMBO J 20:1829–1839Google Scholar
  73. Posey JE, Gherardini FC (2000) Lack of a role for iron in the Lyme disease pathogen. Science 288:1651–1653CrossRefPubMedGoogle Scholar
  74. Recht MI, Douthwaite S, Puglisi JD (1999) Basis for prokaryotic specificity of action of aminoglycoside antibiotics. EMBO J 18:3133–3138PubMedGoogle Scholar
  75. Ren Y-G, Martínez J, Kirsebom LA, Virtanen A (2002) Inhibition of Klenow DNA polymerase and poly(A)-specific ribonuclease by aminoglycosides. RNA 8:1393–1400CrossRefPubMedGoogle Scholar
  76. Rogers J, Chang AH, von Ahsen U, Schroeder R, Davies J (1996) Inhibition of the self-cleavage reaction of the human hepatitis delta virus ribozyme by antibiotics. J Mol Biol 259:916–925CrossRefPubMedGoogle Scholar
  77. Sakon J, Liao HH, Kanikula AM, Benning MM, Rayment I, Holden HM (1993) Molecular structure of kanamycin nucleotidyltransferase determined to 3.0-Å resolution. Biochemistry 32:11977–11984CrossRefPubMedGoogle Scholar
  78. Schlünzen F, Zarivach R, Harms J, Bashan A, Tocilj A, Albrecht R, Yonath A, Franceschi F (2000) Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature 413:814–821Google Scholar
  79. Schroeder R, Waldisch C, Wank H (2000) Modulation of RNA function by aminoglycoside antibiotics. EMBO J 19:1–9PubMedGoogle Scholar
  80. Shi H, Moore PB (2000) The crystal structure of yeast phenylalanine tRNA at 1.93 Å resolution: a classic structure revisited. RNA 6:1091–1105PubMedGoogle Scholar
  81. Stage TK, Hertel KJ, Uhlenbeck OC (1995) Inhibition of the hammerhead ribozyme by neomycin. RNA 1:95–101PubMedGoogle Scholar
  82. Stewart PS, Costerton JW (2001) Antibiotic resistance of bacteria in biofilms. Lancet 358:135–138PubMedGoogle Scholar
  83. Sucheck SJ, Shue YK (2001) Combinatorial synthesis of aminoglycoside libraries. Curr Opin Drug Discov Devel 4:462–470PubMedGoogle Scholar
  84. Sullenger BA, Gilboa E (2002) Emerging clinical applications of RNA. Nature 418:252–258CrossRefPubMedGoogle Scholar
  85. Summers JS, Shimko J, Freedman FL, Badger CT, Sturgess M (2002) Displacement of Mn2+ fromRNA by K+, Mg2+, neomycin B, and an arginine-rich peptide: indirect detection of nucleic acid/ligand interactions using phosphorus relaxation enhancement. J Am Chem Soc 124:14934–149339CrossRefPubMedGoogle Scholar
  86. Sutherland R, Boon RJ, Griffin KE, Masters PJ, Slocombe B, White AR (1985) Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob Agents Chemother 27:495–498PubMedGoogle Scholar
  87. Thompson J, Skeggs PA, Cundliffe E (1985)Methylationof 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea. Mol Gen Genet 201:168–173CrossRefPubMedGoogle Scholar
  88. Tijsterman M, Ketting RF, Plasterk RH (2002) The genetics of RNA silencing. Annu Rev Genet 36:489–519CrossRefPubMedGoogle Scholar
  89. Uhlen P, Laestadius A, Jahnukainen T, Söderblom T, Backhed F, Celsi G, Brismar H, Normark S, Aperia A, Richter-Dahlfors A (2000) Alpha-haemolysin of uropathogenic E. coli induces Ca2+ oscillations in renal epithelial cells. Nature 405:694–697PubMedGoogle Scholar
  90. Van Bambeke F, Glupczynski Y, Plésiat P, Pechère JC, Tulkens PM (2003) Antibiotic efflux pumps in prokaryotic cells: occurrence, impact on resistance and strategies for the future of antimicrobial therapy. J Antimicrob Chemother 51:1055–1065PubMedGoogle Scholar
  91. Vicens Q, Westhof E (2001) Crystal structure of paromomycin docked into the eubacterial ribosomal decoding A site. Structure 9:647–658CrossRefPubMedGoogle Scholar
  92. Vicens Q, Westhof E (2002) Crystal structure of a complex between the aminoglycoside tobramycin and an oligonucleotide containing the ribosomal decoding A site. Chem Biol 9:747–756CrossRefPubMedGoogle Scholar
  93. Vicens Q, Westhof E (2003a) RNA as a drug target: the case of aminoglycosides. Chembiochem 4:1018–1023CrossRefPubMedGoogle Scholar
  94. Vicens Q, Westhof E (2003b) Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide. J Mol Biol 326:1175–1188CrossRefPubMedGoogle Scholar
  95. Vioque A, Arnez J, Altman S (1988) Protein-RNA interactions in the RNase P holoenzyme from Escherichia coli. J Mol Biol 1988 202:835–848CrossRefPubMedGoogle Scholar
  96. Vitreschak AG, Rodionov DA, Mironov AA, Gelfand MS (2004) Riboswitches: the oldest mechanism for the regulation of gene expression? Trends Genet 20:44–50CrossRefPubMedGoogle Scholar
  97. Vogel J, Argaman L, Wagner EGH, Altuvia S (2005) The small RNA IstR inhibits synthesis of an SOS-induced toxic response. Curr Biol 14:2271–2276Google Scholar
  98. von Ahsen U, Davies J, Schroeder R (1991) Antibiotic inhibition of group I ribozyme function. Nature 353:368–370Google Scholar
  99. von Ahsen U, Davies J, Schroeder R (1992) Non-competitive inhibition of group I intron RNA self-splicing by aminoglycoside antibiotics. J Mol Biol 226:935–941Google Scholar
  100. Walsh C (2003) Antibiotics: actions, origins, resistance. ASM press, Washington DCGoogle Scholar
  101. Walter F, Vicens Q, Westhof E (1999) Aminoglycoside-RNA interactions. Curr Opin Chem Biol 3:694–704CrossRefPubMedGoogle Scholar
  102. Walter F, Pütz J, Giegé R, Westhof E (2002) Binding of tobramycin leads to conformational changes in yeast tRNAAsp and inhibition of aminoacylation. EMBO J 21:760–768PubMedGoogle Scholar
  103. Ward A, Campoli-Richards DM (1986) Mupirocin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 32:425–444PubMedGoogle Scholar
  104. Wassarman KM (2003) Diverse regulators of gene expression in response to environmental changes. Cell 109:141–144Google Scholar
  105. Wassarman KM, Storz G (2000) 6S RNA regulates E. coli RNA polymerase activity. Cell 101:613–623CrossRefPubMedGoogle Scholar
  106. Winkler W, Nahvi A, Breaker RR (2002) Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419:952–956CrossRefPubMedGoogle Scholar
  107. Withey JH, Friedman DI (2003) A salvage pathway for protein structures: tmRNA and trans-translation. Annu Rev Microbiol 57:101–123CrossRefPubMedGoogle Scholar
  108. Woegerbauer M, Burgmann H, Davies J, Graninger W (2000) DNase I induced DNA degradation is inhibited by neomycin. J Antibiot (Tokyo) 53:129–137Google Scholar
  109. Yao S, Sgarbi PW, Marby KA, Rabuka D, O’Hare SM, Cheng ML, Bairi M, Hu C, Hwang S-B, Hwang C-K, Ichikawa Y, Sears P, Sucheck SJ (2004) Glyco-optimization of aminoglycosides: new aminoglycosides as novel anti-infective agents. Bioorg Med Chem Lett 14:3733–3738CrossRefPubMedGoogle Scholar
  110. Yonath A, Bashan A (2004) Ribosomal crystallography: initiation, peptide bond formation, and aminoacid polymerization are hampered by antibiotics. Annu Rev Microbiol 58:233–251CrossRefPubMedGoogle Scholar
  111. Zapp ML, Stern S, Green MR (1993) Small molecules that selectively block RNA binding of HIV-1 Rev protein inhibit Rev function and viral production. Cell 74:969–978CrossRefPubMedGoogle Scholar
  112. Zembower TR, Noskin GA, Postelnick MJ, Nguyen C, Peterson LR (1998) The utility of aminoglycosides in an era of emerging drug resistance. Int J Antimicrob Agents 10:95–105PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • L.A. Kirsebom
    • 1
  • A. Virtanen
    • 1
  • N.E. Mikkelsen
    • 2
  1. 1.Department of Cell and Molecular Biology, Biomedical CenterUppsala UniversityUppsalaSweden
  2. 2.Department of Molecular Biology, Biomedical CenterThe Swedish Agricultural UniversityUppsalaSweden

Personalised recommendations