title: The effect of the structure of small cationic peptides on the characteristics of peptide-DNA complexes.
abstract: A series of transcriptional activator (TAT)-protein transduction domains (PTDs) modified with hydrophobic amino acids were used as model cationic amphiphilic peptides to study the effect of hydrophobicity on interaction of such peptides with plasmid DNA. The peptide-DNA complexes were analyzed by dynamic light scattering and gel electrophoresis to determine their size and electrokinetic properties at various +/- charge ratios. Peptides in solution were found to have a tendency to aggregate and the hydrodynamic size of the aggregates depends on the structure of peptide. Peptides with smaller hydrophobic residues at the N-terminal formed smaller complexes with DNA compared to the ones with larger hydrophobic tails. DNA complexes having peptides with more than one hydrophobic moiety at the N-terminal had a tendency to aggregate. Among the peptides having single hydrophobic amino acid at the N-terminal, DNA complexes of Tyr-TAT and Phe-TAT were found to be stable in solution. The size of the hydrophobic domain and the type of hydrophobic amino acid at the N-terminal of cationic amphiphilic peptides play an important role not only in the complex formation but also in stabilizing the system. The studies presented here indicate that there is a potential for strategic development of these peptides into potential non-viral gene delivery vectors.
authors.affiliation: The University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USA.
authors.forename: Geetha N
authors.initials: GN
authors.lastname: Goparaju
authors.forename: C
authors.initials: C
authors.lastname: Satishchandran
authors.forename: Pardeep K
authors.initials: PK
authors.lastname: Gupta
mesh_terms: D000595:Amino Acid Sequence; D002412:Cations / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage*; D004587:Electrophoresis, Agar Gel; D015696:Gene Products, tat / Q000737:chemistry*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D010957:Plasmids / Q000008:administration & dosage; D012542:Scattering, Radiation
chemical_list: D002412:Cations; D015696:Gene Products, tat; D010455:Peptides; D004247:DNA