Polymyxin and related peptide antibiotics

Annu Rev Biochem. 1977;46:723-63. doi: 10.1146/annurev.bi.46.070177.003451.

Abstract

The general mechanism for the antibiotic activities of the polymyxins and octapeptins has been elucidated by research using a broad range of experimental techniques. However, this phenomenon has not been described in detailed molecular terms, and this must be one of the major goals for future research in this area. Since 1947, when polymyxin was first isolated, there have been tremendous advances in our knowledge of membrane structure. The application of biophysical technology such as NMR, ESR, fluorescence spectroscopy, differential scanning calorimetry, and electron microscopy has been particularly valuable for studying model and biological membrane structures. It is these techniques which will provide a detailed molecular mechanism for the effects of these peptide antibiotics on membrane structure. In addition, the large number of antibiotic derivatives available should be exploited more extensively for structure-function correlations. The ultimate goal is to correlate the biological properties of these peptides with their effects on the physical properties of membranes and to rationalize these events in terms of lipid-peptide interactions.

Publication types

  • Review

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Anti-Bacterial Agents* / pharmacology
  • Bacillus subtilis / drug effects
  • Bacillus subtilis / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Membrane Permeability / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Escherichia coli / drug effects
  • Lipopolysaccharides / physiology
  • Liposomes
  • Membranes, Artificial
  • Models, Biological
  • Oligopeptides / pharmacology
  • Oxygen Consumption / drug effects
  • Peptides, Cyclic / pharmacology
  • Phospholipids / physiology
  • Polymyxins* / pharmacology
  • Protein Binding
  • Pseudomonas aeruginosa / drug effects
  • Species Specificity
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Lipopolysaccharides
  • Liposomes
  • Membranes, Artificial
  • Oligopeptides
  • Peptides, Cyclic
  • Phospholipids
  • Polymyxins
  • Adenosine Triphosphate