Amphipathic cyclooctapeptides: interactions with detergent micelles and metal ions

In order to study the secondary structural preferences of amphipathic cyclopeptides in detergent assemblies and their interactions with metal ions, two basic amphiphatic cyclooctapeptides, c[(Lys-d-Lys)2-Xaa-d-Leu-Leu-d-Leu], where Xaa is Leu (P1) or Trp (P2), were studied by circular dichroism (CD) spectroscopy. In water, P1 exhibited an unordered secondary structure whereas P2 adopted a partial β-sheet structure. Temperature effect on the CD of these cyclopeptides showed small changes over the temperature range from 278 to 353 K. P1 showed low and non-specific binding affinity for metal ions (Ca2+, Zn2+, Na+, or Li+) in water whereas P2 did not exhibit any significant interaction with these ions. However, in the zwitterionic micellar detergent dodecylphosphocholine (DPC), P2 adopted a β-sheet structure, which exhibited a greater propensity for metal ion interactions (K1∼103 M−1 and K2∼102 M−1). Variable temperature CD studies on the peptide-metal ion complexes showed that these interactions are thermally reversible. Our results indicate that amphipathic cyclooctapeptides can co-assemble with micellar DPC and are capable of interacting with metal ions. This study will improve our ability to design a better metal ion sensing cyclopeptide in co-micellar assembles.