Interaction of phospholipid Langmuir monolayers with an antibiotic peptide conjugate.

The interactions between phospholipid monolayers and a peptide conjugate of the antituberculotic agent isoniazide (INH) were investigated by sum-frequency vibrational spectroscopy. The primary objective of the present work was to provide a detailed picture of the molecular interactions of the INH-peptide conjugate with phospholipid monolayers by detecting the changes in the monolayer structure resulting from these interactions. In order to gain a thorough understanding, three types of experiment were performed: (i) changes induced in the structure of the precompressed phospholipid monolayer upon injection of the INH-peptide conjugate were followed; (ii) the structures of the phospholipid monolayers spread onto the solution of the INH-peptide conjugate were characterized; (iii) the structures of mixed monolayers of phospholipid and the INH-peptide conjugate were studied. Using a chain perdeuterated phospholipid, it was possible to examine the changes in alkyl chain ordering without interference from INH-peptide conjugate vibrations and investigate the effect of the INH-peptide conjugate on the ordering of the phosphocholine headgroups. We confirmed that peptide conjugation strongly influences the interactions of INH with the lipid monolayer, resulting in enhanced cell penetration ability. The interactions formed between the INH-peptide conjugate in its ordered adsorption layer and the phospholipid molecules deposited onto this solution were found to be significantly stronger than those formed by the INH-peptide conjugate with a compressed lipid monolayer. Nonetheless, both types of interaction contribute with a condensing effect to an increased ordering of the phospholipid alkyl chains in the monolayer.

Membrane affinity and antibacterial properties of cationic polyelectrolytes with different hydrophobicity.

The antibacterial behavior of cationic polyelectrolytes is studied using model membrane experiments and in vitro bacterial investigations. The molecular interaction with lipid films is evaluated by the degree of penetration of the polymers into Langmuir monolayers of neutral or negatively charged lipids. The polymer/lipid interaction results in structural changes of the penetrated lipid layer visualized using AFM. The polymers are found to be effective in inhibiting the proliferation of E. coli, B. subtilis and S. aureus. The influence of the chemical structure on the functional behavior is related to the conformational properties. An optimum structure is identified on the basis of antibacterial and hemolytic tests as well as membrane-destroying efficacy of the antimicrobial polymers.

Characterisation of the membrane affinity of an isoniazide peptide conjugate by tensiometry, atomic force microscopy and sum-frequency vibrational spectroscopy, using a phospholipid Langmuir monolayer model.

Tensiometry, sum-frequency vibrational spectroscopy, and atomic force microscopy were employed to assess the cell penetration ability of a peptide conjugate of the antituberculotic agent isoniazide. Isoniazide was conjugated to peptide (91)SEFAYGSFVRTVSLPV(106), a functional T-cell epitope of the immunodominant 16 kDa protein of Mycobacterium tuberculosis. As a simple but versatile model of the cell membrane a phospholipid Langmuir monolayer at the liquid/air interface was used. Changes induced in the structure of the phospholipid monolayer by injection of the peptide conjugate into the subphase were followed by tensiometry and sum-frequency vibrational spectroscopy. The drug penetrated lipid films were transferred to a solid support by the Langmuir-Blodgett technique, and their structures were characterized by atomic force microscopy. Peptide conjugation was found to strongly enhance the cell penetration ability of isoniazide.