title: N-acyl-(alpha, gamma diaminobutyric acid)n hydrazide as an efficient gene transfer vector in mammalian cells in culture.
abstract: OBJECTIVE
  This study investigates the structure/activity relationship of a series of N-acyl-peptides (lipopeptides) for the transfection of mammalian cells.
  
  
  METHODS
  Lipopeptides comprising 1 to 3 basic amino-acids and a single fatty acid chain were synthesized. Transfecting complexes between lipopeptide, plasmid DNA and dioleoyl phosphatidylethanolamine were prepared and applied on cells in culture. Transfection efficiency was evaluated by measuring beta-galactosidase activity 48 h post-transfection. Lipopeptide-DNA binding was also investigated by physical means and molecular modelling.
  
  
  RESULTS
  Besides the length of the fatty acid chain, the nature of the basic amino-acid and the C-terminal group were crucial parameters for high transfection efficiency. The N-acyl-(diaminobutyric acid)n derivatives were the most potent transfecting agents among those tested and induced a beta-galactosidase activity 2 to 20 times higher than the N-acyl-lysine, -ornithine or -diaminopropionic acid derivatives. Furthermore, a hydrazide C-terminal modification greatly enhanced transfection efficiency for all compounds tested. The reason why alpha, gamma-diaminobutyric acid hydrazide-based lipopeptides were the most potent in transfection is not fully understood but could be related to their high DNA binding.
  
  
  CONCLUSIONS
  Poly- or oligo-diaminobutyric acid containing or not a hydrazide C-terminus could advantageously be used in peptide-based gene delivery systems.
authors.affiliation: Pharma Division, F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: J Y
authors.initials: JY
authors.lastname: Legendre
authors.forename: A
authors.initials: A
authors.lastname: Trzeciak
authors.forename: D
authors.initials: D
authors.lastname: Bur
authors.forename: U
authors.initials: U
authors.lastname: Deuschle
authors.forename: A
authors.initials: A
authors.lastname: Supersaxo
mesh_terms: D000613:Aminobutyrates / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D000882:Haplorhini; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008958:Models, Molecular; D010957:Plasmids; D014162:Transfection
chemical_list: D000613:Aminobutyrates; D006834:Hydrazines