Synthesis of a Highly Hydrophobic Cationic Lipid and Structural and Thermodynamic Studies for Interaction with DNA

• Published in: Bulletin of the Chemical Society of Japan 2010-09, Vol.83 (9), p.1010-1018
• Main Authors: Nishimura, Tomoki, Cho, Takeshi, Kelley, Andrew M, Powell, Magdalena E, Fossey, John S, Bull, Steven D, James, Tony D, Masunaga, Hiroyasu, Akiba, Isamu, Sakurai, Kazuo
• Format: Article
• Language: English
• Subjects: Aromatics
• ISSN: 0009-2673; 1348-0634; 1348-0634
• DOI: 10.1246/bcsj.20100072

Synthetic DNA-transfection reagents can overcome safety issues raised by use of viral DNA vectors. One of these candidates is a cationic lipid that can form a supramolecular complex with DNA. We have been working in a series of aromatic diamine lipids with different tail length from C6 to C18: [N-(3,5-dialkylbenzyl)ethane-1,2-diamine, denoted DA] as such a lipid. The present paper describes the synthesis and the fundamental properties of DA. SAXS from DA solution showed bilayer vesicle formation, while it showed lamellar formation after the complexation with DNA. When we measured the N/P ratio (molar ratio of the amine groups (N) in DA to phosphate groups (P) in the DNA) dependence of SAXS, the lamellar peak (spacing = 5.0 nm) increased proportionally to the added DNA concentration at N/P ≥ 8. On the other hand, in the range of N/P < 8, the spacing was increased to 5.5 nm and the area decreased as DNA increased. These different features between N/P ≥ 8 and N/P < 8 suggest that the lamellar supramolecular structures differ according to the composition.