With contributions by numerous experts

Klappentext

With contributions by numerous experts

Inhalt

1 The Naturally Occurring Aminoglycoside Antibiotics.- A. Introduction.- B. Aminoglycoses and Noncyclitol Aminoglycosides.- I. Aminoglycose Derivatives.- II. Disaccharides and Pseudodisaccharides.- III. Trisaccharides.- C. Aminocyclitol Aminoglycosides Containing Streptamine, 2-Deoxystreptamine, or Their Derivatives.- I. Monosubstituted Streptamine and 2-Deoxystreptamine Aminoglycosides.- 1. 4- or 6-Substituted Cyclitol.- 2. 5-Substituted Cyclitol.- II. Disubstituted 2-Deoxystreptamine Aminoglycosides.- 1. 4,5-Disubstituted Cyclitol.- 2. 4,6-Disubstituted Cyclitol.- III. 1-N-Acyl Substituted Cyclitol.- D. Aminoglycosides with Cyclitol Aglycones Other than Streptamine or 2-Deoxystreptamine.- I. Nonbasic Cyclitol.- II. Monoaminocyclitol.- III. Diaminocyclitol.- References.- 2 Total Synthesis and Chemical Modification of the Aminoglycoside Antibiotics.- A. Introduction.- B. Several Reactions and Methods Generally Useful for the Synthesis of Aminoglycoside Antibiotics.- I. Simultaneous Protection of Vicinal Trans-Equatorial Amino and Hydroxyl Groups.- II. Selective Cyclic Acetalation.- III. 1,2-cis-Glycosylation of Aminosugars.- IV. Selective Deoxygenation Reactions.- 1. 3-Deoxygenation.- 2. 3,4-Dideoxygenation.- V. Selective N-Protection via Temporary Metal Chelation of Vicinal and Nonvicinal Amino-Hydroxy or Amino-Amino Groups.- VI. Determination of the Configurations of Aminopyranosides and Aminocyclitols by the Shift in Optical Rotation Due to Copper(II) Chelate Formation.- C. Total Synthesis and Modification of Aminoglycoside Antibiotics.- I. Streptomycin Group.- 1. Total Synthesis of Streptomycin and Dihydrostreptomycin.- 2. Chemical Modification of Streptomycin and Dihydrostreptomycin.- II. Pseudodisaccharides Containing 4-Substituted 2-Deoxystreptamine - Paromamine, Neamine, and Related Compounds.- 1. Synthesis of Paromamine and Neamine.- 2. Deoxygenated Derivatives.- 3. Epimerized Derivatives.- 4. Amino-Deoxy Derivatives.- 5. Derivatives Having a Side Chain or Longer Chain.- 6. 1-N-Acyl Derivatives.- 7. Other Derivatives.- III. Pseudotrisaccharides Containing 4,5-Disubstituted 2-Deoxystreptamine - Ribostamycin, Butirosins, and Related Compounds.- 1. Synthesis of Ribostamycin and Related Pseudotrisaccharides.- 2. Deoxy Derivatives.- 3. 1-N-Acyl and 1-N-Alkyl Derivatives of 4,5-Disubstituted Pseudotrisaccharides.- IV. Pseudotetra- and Pseudopentasaccharides Containing 4,5-Disubstituted 2-Deoxystreptamine - Neomycins, Paromomycins, Lividomycins, and Related Compounds.- 1. Total Synthesis of Neomycin C.- 2. Synthesis of Analogs of Neomycin, Paromomycin, and Lividomicin B.- 3. Amino-Deoxy Derivatives.- 4. N-Alkyl Derivatives.- 5. 1-N-Acyl Derivatives.- V. Pseudotrisaccharides Containing 4,6-Disubstituted 2-Deoxystreptamine - Kanamycin, Tobramycin, Gentamicin, and Related Compounds.- 1. Kanamycins and Their Derivatives.- 2. Gentamicins and Related Compounds.- 3. Sisomicin, Its Derivatives, and Related Unsaturated Compounds.- 4. 1-N-Acylgentamicins and 1-N-Acylsisomicins.- 5. Seldomycin Modifications.- 6. Other 4,6-Disubstituted Derivatives.- VI. Other Groups.- 1. Kasugamycin and Its Modifications.- 2. Spectinomycin Group.- 3. Fortimicins, Istamycins, and Related Compounds.- 4. Sorbistins and Analogs.- 5. Minosaminomycin.- 6. Alpha,Alpha-Trehalosamine.- References.- 3 Biosynthesis and Mutasynthesis of Aminoglycoside Antibiotics.- A. Introduction.- I. Historical Background.- II. Methodology.- 1. Application of Labeled Compounds.- 2. Application of Cell-Free Extracts of Mycelia or Enzymes.- 3. Application of Mutants.- III. Plasmid Involvement.- 1. General Aspects.- 2. Plasmid Involvement in Aminoglycoside Synthesis.- 3. Experimental Methods.- B. Biosynthesis of Major Aminoglycosides.- I. Streptomycin and Bluensomycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Correlation with Cell Wall Biosynthesis.- 4. Plasmid Involvement.- II. Neomycin and Paromomycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Plasmid Involvement.- III. Ribostamycin, Xylostasin, and Butirosin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Glucosamine Auxotroph and Butirosin Biosynthesis.- 4. Plasmid Involvement.- IV. Kanamycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Plasmid Involvement.- V. Gentamicin and Sisomicin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- VI. Spectinomycin (Actinospectacin).- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- VII. Kasugamycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- 3. Plasmid Involvement.- VIII. Validamycin.- 1. Biosynthesis of Subunits.- 2. Subunit Assembly.- IX. Miscellaneous Aminoglycosides.- 1. 1,4-Diaminocyclitol Aminoglycosides.- 2. Monoaminocyclitol Aminoglycosides.- 3. Apramycin.- X. Comprehensive Discussion on the Biosynthesis of Aminoglycosides.- C. Mutational Biosynthesis (Mutasynthesis).- D. Conclusion.- References.- 4 Antibacterial Activity of Aminoglycoside Antibiotics.- A. Introduction.- B. Drug Resistance Plasmids.- I. The Discovery of R Factors.- II. The Discovery of Nonconjugative Resistance (r) Plasmids.- C. Resistance Patterns of Bacteria.- D. Bacterial Strains Resistant to Aminoglycoside Antibiotics.- I. Drug Resistance Mediated by R Plasmids.- II. Antibacterial Activity of Aminoglycoside Antibiotics.- E. Conclusion.- References.- 5 Mechanism of Action of Aminoglycoside Antibiotics.- A. The Effects on Bacterial Cells and Their Components.- I. In vivo Effects on Bacteria in Relation to Mode of Action.- II. Interference with Protein Synthesis in vitro.- III. Localization of Drug Sensitivity, Resistance, and Dependence on the Ribosome.- IV. Interaction with Ribosomes and Ribosomal Components.- 1. Binding of Streptomycin to the Ribosome and Ribosomal Subunits.- 2. Binding Site of Streptomycin on the Ribosome.- 3. Binding of Kanamycin to the Ribosome and Ribosomal Subunits.- 4. Binding of Other Aminoglycosides to the Ribosome and Ribosomal Subunits.- V. Interference with Ribosomal Functions.- 1. Inhibition of Initiation of Protein Synthesis.- 2. Chain Elongation Processes Affected.- 3. Interference with Termination.- VI. Interaction with Bacterial Cell Envelope.- 1. Membrane Damage.- 2. Uptake of Streptomycin by Bacterial Cells.- 3. Drug Resistance Due to Transport Barriers.- VII. Structure-Activity Relationships.- 1. Structure Required for Codon Misreading Activity.- 2. Structure Needed for the Inhibition of Translocation.- B. Effects on Mammalian or Eukaryotic Cells and Their Components.- I. Interaction with Ribosomes and Interference with Ribosomal Functions.- II. Interaction with Tubulin and Microtubules.- III. Interaction with Actin.- IV. Interaction with Membrane or Phospholipid.- C. Peptide Antibiotics Showing Similar Mechanisms of Inhibition of Ribosomal Functions.- I. Viomycin.- 1. Inhibition of Protein Synthesis.- 2. Binding to Ribosomes and Ribosomal Subunits.- 3. Localization of Drug Resistance in the Ribosome.- 4. Mechanism of Translocation Inhibition.- II. Negamycin.- D. Discussion.- E. Summary.- I. Localization of Drug Sensitivity, Resistance, and Dependence on the Ribosome.- II. Binding of Aminoglycosides to the Ribosome.- III. Inhibition of Initiation of Protein Synthesis.- IV. Stimulation of Codon Misreading.- V. Interference with Aminoacyl-tRNA Binding.- VI. Inhibition of Translocation of Peptidyl-tRNA.- VII. Interference with Termination of Protein Synthesis.- VIII. The Effects on Cell Membrane.- IX. Uptake of Aminoglycosides by Bacterial Cells.- X. Effects on Mammalian or Eukaryotic Cell Components.- References.- 6 Mechanisms of Resistance to Aminoglycoside Antibiotics.- A. Introduction.- B. Biochemical Mechanisms of Resistance.- I. Discovery of Enzymes Involved in Resistance.- II. Resistance to 2-Deoxystreptamine-Containing Antibiotics.- 1. 3?-Phosphotransferase [APH (3?)].- 2. 5?-Phosphotransferase [APH (5…