caa a22 4500 47712805X CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012105128722 doi (NATIONALLICENCE)springer-10.1023/A:1012105128722 N-Acyl-(α,γ Diaminobutyric Acid)n Hydrazide as an Efficient Gene Transfer Vector in Mammalian Cells in Culture [Elektronische Daten] [Jean-Yves Legendre, Arnold Trzeciak, Daniel Bur, Ulrich Deuschle, Andreas Supersaxo] 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 β-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 β-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 α, γ-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. Plenum Publishing Corporation, 1997 transfection nationallicence gene therapy nationallicence peptide nationallicence diaminobutyric acid nationallicence hydrazide nationallicence DNA nationallicence Legendre Jean-Yves Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut Trzeciak Arnold Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut Bur Daniel Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut Deuschle Ulrich Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut Supersaxo Andreas Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 619-624 0724-8741 14:5<619 1997 14 11095 https://doi.org/10.1023/A:1012105128722 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012105128722 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Legendre Jean-Yves Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Trzeciak Arnold Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Bur Daniel Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Deuschle Ulrich Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut NATIONALLICENCE 700 1- Supersaxo Andreas Pharma Division, Preclinical Research and Development, F. Hoffmann-La Roche AG, CH-4070, Basel, Switzerland aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 619-624 0724-8741 14:5<619 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer