N-acyl-(alpha, gamma diaminobutyric acid)n hydrazide as an efficient gene transfer vector in mammalian cells in culture.
Pharm Res
; 14(5): 619-24, 1997 May.
Article
em En
| MEDLINE
| ID: mdl-9165533
ABSTRACT
PURPOSE:
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Técnicas de Transferência de Genes
/
Vetores Genéticos
/
Aminobutiratos
/
Hidrazinas
Limite:
Animals
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
1997
Tipo de documento:
Article