N4,N9-Dioleoyl Spermine Is a Novel Nonviral Lipopolyamine Vector for Plasmid DNA Formulation

Abstract

N4,N9-Dioleoyl spermine condenses DNA and achieves high transfection levels in cultured cells.

Very Long Chain N 4 ,N 9 -Diacyl Spermines: Non-Viral Lipopolyamine Vectors for Efficient Plasmid DNA and siRNA Delivery

“…NH 3 200:10:1 to 100:10:1 to 50:10:1; v/v/v). N 4 ,N 9 -Dioleoyl-1,12-diamino-4,9-diazadodecane 1 Prepared via N 1 ,N 12 -ditrifluoroacetyl-N 4 ,N 9 -dioleoyl-1,12-diamino-4,9-diazadodecane (36), the target lipopolyamine displayed HRMS: found (m/z [M+H] + ) 731.7115, C 46 H 91 N 4 O 2 requires 731.7142 (Δ ppm 3.7), consistent with the data previously reported (2,3).…”

“…So this facile and specific introduction of trifluoroacetyl, using ethyl trifluoroacetate, makes it a superior protecting group to carbobenzoxy (Z, CBZ) and to tert-butoxycarbonyl (Boc) for the purpose of gram scale protection of polyamines (42). Thus, trifluoroacetyl is the protecting group of choice, over Z and Boc, for practical routes to polyamine amides (2,3,42). Therefore, using this strategy, we chemo-selectively protected the two primary amines of spermine then, without purification, aliphatic acyl chains were added.…”

“…Our NVGT focus is on lipopolyamines composed of two long-carbon chains (or a steroid) covalently bound to a polyamine e.g. spermine (1,12-diamino-4,9-diazadodecane) (2,3). Other research groups are investigating a variety of alternative approaches, including: naked polynucleotides, gene gun (bound to gold particles), electroporation, and the use of a wide variety of cationic lipids (lipoplexes) (4)(5)(6)(7)(8) and cationic polymers (polyplexes), for reviews see: (9)(10)(11)(12).…”

“…Our aims are to design and develop efficient, non-toxic, non-viral vectors for in vitro and possible in vivo applications, using our novel spermine conjugates, based on change to the type, length, position, and number of the hydrophobic anchors (2,3). These cationic lipids (lipospermines) probably assist in the self-assembling of polycationic scaffolds, as well as facilitating absorptive endocytosis and/or fusion with cell membranes.…”

“…Ghonaim, Li and Blagbrough groups in our synthesis of polyamine conjugates with regiochemical control (2,3,42). The yield for this deprotection step was increased to 80% by using K 2 CO 3 (1.5 eq.)…”