Aminoglycoside-Derived Cationic Lipids for Gene Transfection: Synthesis of Kanamycin A Derivatives

• Published in: European journal of organic chemistry Vol. 2003; no. 15; pp. 2764 - 2774
• Main Authors: Sainlos, Matthieu, Belmont, Philippe, Vigneron, Jean-Pierre, Lehn, Pierre, Lehn, Jean-Marie
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.08.2003; WILEY‐VCH Verlag; Wiley
• Subjects: Aminoglycosides; Cationic lipids; Chemistry; Chemistry, Organic; Gene transfer; Nonviral vectors; Physical Sciences; Science & Technology; ANTIBIOTICS; TAR RNA; gene transfer; COMPLEXES; GUANIDINIUM-CHOLESTEROL; DELIVERY; IN-VITRO; MAGNETIC-RESONANCE-SPECTROSCOPY; INHIBITION; cationic lipids; EFFICIENT VECTORS; N-ALKYLATION; aminoglycosides; nonviral vectors
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200300164

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)