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.