Membrane structure and interactions of peptide hormones with model lipid bilayers

In this work, the behavior of the neurohypophyseal hormones and their selected analogs was studied in the presence of membrane models in an attempt to correlate their activities with a distinct behavior at a level of peptide–lipid interactions. The influence of the peptides studied on the lipid acyl chain order was determined using FTIR spectroscopy. Conformational changes in the peptides upon binding to liposomes were examined using CD spectra. Attempts were also made to determine the binding parameters of the peptides to lipids using isothermal titration calorimetry (ITC). The results show unambiguously that the neurohyphophyseal hormone-like peptides interact with lipids, being a model of a eukaryotic cell membrane. Moreover, hydrophobic interactions between the peptides and liposomes are likely to determine the overall conformation of the peptide, especially below the temperature of the main phase transition (Tm). Thus, the bulky and hydrophobic nature of the residues incorporated into the N-terminal part of neurohyphophyseal hormones is an important factor for both restriction of peptide mobility and the interaction of the analog with biomembrane. In turn, above Tm, the electrostatic interactions become also relevant for the conformation of the acyclic tail of the AVP-like peptides. ⺠The behavior of the AVP and OT-like peptides at a level of peptide–lipid interactions. ⺠The hydrophobic modification improves the peptide insertion into the lipid bilayer. ⺠The hydrophobic interactions between the peptides and liposomes determine the overall conformation of the peptide. ⺠The electrostatic interactions become relevant for the AVP-like peptides above Tm.