Aminoglycoside-derived cationic lipids for gene transfection: Synthesis of kanamycin A derivatives

Cationic lipids are currently actively investigated as an alternative approach to recombinant viruses for gene transfer studies and gene therapy applications. Basically, they rely on the formation of lipid/DNA aggregates via electrostatic interactions between their cationic headgroup and the negatively charged DNA. The development of new amphiphilic structures should allow to shed light on their still poorly understood structure/activity relationship and thereby help to design improved vectors. It appears that aminoglycosides, which are natural polyamines known to bind to nucleic acids, provide a favourable scaffold for the synthesis of a variety of cationic lipids because of their structural features and multifunctional nature. The synthesis and full characterization of a series of lipophilic derivatives of the aminoglycoside antibiotic kanamycin A, mainly kanamycin-cholesterol conjugates, are reported herein. © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.