title: Nanofibers resulting from cooperative electrostatic and hydrophobic interactions between peptides and polyelectrolytes of opposite charge.
abstract: We investigated whether cationic peptides that contain hydrophobic side chains were able to stabilize themselves via hydrophobic interactions between neighboring peptide molecules upon electrostatic binding to oppositely charged polyelectrolytes. The interaction mechanism was examined through a model system consisting of the anionic polyelectrolyte alginate and the cationic decapeptide ozarelix. The interaction resulted in the formation of highly ordered complexes that were noticeable upon visual inspection. These complexes were then investigated by microscopic techniques and shown to exhibit a branched network structure. Cryogenic-temperature transmission electron microscopy (cryo-TEM) and negative staining TEM revealed that the molecular interactions between alginate and ozarelix led to the formation of nanofibers. The rodlike nanofibers had a diameter distribution of 4-8 nm. Isothermal titration calorimetry was used to determine the thermodynamic parameters of the alginate-ozarelix interaction. The binding constant was found to be on the order of 10(6) M(-1), indicating a high binding affinity. The interaction of the peptide with the polyelectrolyte triggered profound changes in the conformation of ozarelix, which was confirmed by UV spectroscopy and circular dichroism. On the basis of these experimental results, a theoretical modeling study of the alginate-ozarelix interaction was conducted to gain a better molecular-level understanding of the complex structure. It revealed that, upon binding of ozarelix to alginate, new intermolecular and intramolecular aromatic interactions between the ozarelix molecules occurred. These interactions changed the conformation of the peptide, a modification in which the aromatic side chains played a major role. Our results indicate that the cationic peptides interact with the polyanions via electrostatic interactions, but are additionally stabilized via hydrophobic interactions. This binding mode may serve as a powerful tool to extend the duration of drug release in hydrogel drug delivery systems.
authors: Department of Pharmaceutical Technology, University of Regensburg, 93053 Regensburg, Germany.
authors: Matthias
authors: M
authors: Ferstl
authors: Andrea
authors: A
authors: Strasser
authors: Hans-Joachim
authors: HJ
authors: Wittmann
authors: Markus
authors: M
authors: Drechsler
authors: Matthias
authors: M
authors: Rischer
authors: Jürgen
authors: J
authors: Engel
authors: Achim
authors: A
authors: Goepferich
mesh_terms: D004573:Electrolytes / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008968:Molecular Conformation; D057139:Nanofibers / Q000737:chemistry*; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D055672:Static Electricity; D013499:Surface Properties
chemical_list: D004573:Electrolytes; D010455:Peptides; D011108:Polymers