Studies on the aggregation and possible channel formation in membranes of a cyclic hexapeptide, cyclo (d‐Ala‐l‐Pro‐l‐Ala)₂

Abstract

The interaction of zwitterionic lipid DMPC and DPPC with cyclic hexapeptide, cyclo (D-Ala-L-Pro-L-Ala)2 was studied using circular dichroism (CD) and differential scanning calorimetry (DSC). Preliminary membrane conductance results showed that the peptide has a tendency to form channels inside the lipid bilayer. CD studies indicated that as the lipid/peptide (L/P) ratio (DMPC/peptide) was increased, the magnitude of the negative CD band having a lambda(max) around 200 nm decreased. At a L/P ratio of 210:1, this band disappeared completely, indicating dramatic conformational changes in the peptide on interaction with the lipid bilayer. Reduction of the phase transition temperature and the maximum heat capacity of the lipid bilayer (DPPC) for gel-to-liquid crystalline phase transition indicates a strong interaction of the peptide with the lipid bilayer.

Study of (Cyclic Peptide)–Polymer Conjugate Assemblies by Small‐Angle Neutron Scattering

“…who observed electron (and optical) microscopy images of unconjugated CPs in bundles (microcrystals) . We interpret the SANS patterns to mean that CP1 exists as bundles of short tubes in [D 6 ]DMSO, a concept that has also been proposed in the study of CP ion channel mechanism . Indeed, although early work in the field presented the mechanism of ion transport through the internal cavities of cyclic peptide nanotubes, assembly into ‘barrel and stave’ structures has also been suggested .…”

“…and Kodama et al. have shown that the transport of ions is possible with cyclic peptides with only 4 or 6 residues, for which the internal pore is too small to allow ion transport, thus suggesting a barrel and stave assembly …”