title: Coiled coil peptides and polymer-peptide conjugates: synthesis, self-assembly, characterization and potential in drug delivery systems.
abstract: Coiled coils are a common structural motif in many natural proteins that can also be utilized in the design and preparation of drug delivery systems for the noncovalent connection of two macromolecules. In this work, two different pairs of peptides forming coiled coil hetero-oligomers were designed, synthesized, and characterized. While the peptide sequences (VAALEKE)4 and (VAALKEK)4 predominantly form coiled coil heterodimers with randomly orientated peptide chains, (IAALESE)2-IAALESKIAALESE and IAALKSKIAALKSE-(IAALKSK)2 tend to form higher hetero-oligomers with an antiparallel orientation of their peptide chains. The associative behavior of these peptides was studied in aqueous solutions using circular dichroism spectroscopy, size-exclusion chromatography, isothermal titration calorimetry and sedimentation analyses. The orientation of the peptide chains in the coiled coil heterodimers was assessed using fluorescence spectroscopy with fluorescence resonance energy transfer labels attached to the ends of the peptides. The formation of the heterodimer can be used as a general method for the selective noncovalent conjugation of a specific targeting moiety with various drug carrier systems; this process involves simple self-assembly in a physiological solution before drug administration. The preparation of targeted macromolecular therapeutics consisting of a synthetic polymer drug carrier and a recombinant protein targeting ligand is discussed.
authors.affiliation: Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic , Heyrovskeho nam. 2, 16206 Prague 6, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Pechar
authors.forename: Robert
authors.initials: R
authors.lastname: Pola
authors.forename: Richard
authors.initials: R
authors.lastname: Laga
authors.forename: Alena
authors.initials: A
authors.lastname: Braunová
authors.forename: Sergey K
authors.initials: SK
authors.lastname: Filippov
authors.forename: Anna
authors.initials: A
authors.lastname: Bogomolova
authors.forename: Lucie
authors.initials: L
authors.lastname: Bednárová
authors.forename: Ondřej
authors.initials: O
authors.lastname: Vaněk
authors.forename: Karel
authors.initials: K
authors.lastname: Ulbrich
mesh_terms: D000595:Amino Acid Sequence; D004337:Drug Carriers / Q000737:chemistry*; D008689:Methacrylates / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D060327:Solid-Phase Synthesis Techniques
chemical_list: D004337:Drug Carriers; D008689:Methacrylates; D009842:Oligopeptides; C032802:hydroxypropyl methacrylate