title: Temperature dependence of the binding of endotoxins to the polycationic peptides polymyxin B and its nonapeptide.
abstract: The interaction between endotoxins-free lipid A and various lipopolysaccharide (LPS) chemotypes with different sugar chain lengths-and the polycationic peptides polymyxin B and polymyxin nonapeptide has been investigated by isothermal titration calorimetry between 20 and 50 degrees C. The results show a strong dependence of the titration curves on the phase state of the endotoxins. In the gel phase (<30 degrees C for LPS and <45 degrees C for lipid A), an endothermic reaction is observed, for which the driving force is an entropically driven endotoxin-polymyxin interaction, due to disruption of the ordered water structure and cation assembly in the lipid A backbone and adjacent molecules. In the liquid crystalline phase (>35 degrees C for LPS and >47 degrees C for lipid A) an exothermic reaction takes place, which is mainly due to the strong electrostatic interaction of the polymyxins with the negative charges of the endotoxins, i.e., the entropic change DeltaS is much lower than in the gel phase. For endotoxins with short sugar chains (lipid A, LPS Re, LPS Rc) the stoichiometry of the polymyxin binding corresponds to pure charge neutralization; for the compounds with longer sugar chains (LPS Ra, LPS S-form) this is no longer valid. This can be related to the lower susceptibility of the corresponding bacterial strains to antibiotics.
authors.affiliation: Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, D-23845 Borstel, Germany. kbranden@fz-borstel.de
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.forename: Alexander
authors.initials: A
authors.lastname: David
authors.forename: Jörg
authors.initials: J
authors.lastname: Howe
authors.forename: Michel H J
authors.initials: MH
authors.lastname: Koch
authors.forename: Jörg
authors.initials: J
authors.lastname: Andrä
authors.forename: Patrick
authors.initials: P
authors.lastname: Garidel
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D023181:Antimicrobial Cationic Peptides / Q000032:analysis / Q000737:chemistry; D001665:Binding Sites; D003460:Crystallization / Q000379:methods; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry*; D046911:Macromolecular Substances / Q000032:analysis / Q000737:chemistry; D008968:Molecular Conformation; D044367:Phase Transition; D011073:Polyamines; D000071228:Polyelectrolytes; D011112:Polymyxin B / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry*; D011485:Protein Binding; D012475:Salmonella / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013696:Temperature
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008050:Lipid A; D008070:Lipopolysaccharides; D046911:Macromolecular Substances; D011073:Polyamines; D000071228:Polyelectrolytes; D011112:Polymyxin B; C038934:polymyxin B nonapeptide