Open AccessSynthesis, self-assembly and lipoplex formulation of two novel cyclic phosphonate lipids
Author(s) -
Jennifer Yeh,
Elena Tamarkina,
Nada Abdul Khalique,
Liji Raju,
Michael D. Pungente
Publication year - 2012
Publication title -
qscience connect
Language(s) - English
Resource type - Journals
ISSN - 2223-506X
DOI - 10.5339/connect.2012.6
Subject(s) - phosphonate , chemistry , critical micelle concentration , cationic polymerization , diastereomer , dna , micelle , stereochemistry , organic chemistry , combinatorial chemistry , biochemistry , aqueous solution
Background: Synthetic cationic lipids hold much potential as gene packaging and delivery agents for the treatment of inherited and acquired life threatening diseases, such as cancer, AIDS, cardiovascular diseases, and certain autoimmune disorders. Methods: We report the synthesis, self-assembly as characterized by critical micelle concentrations and plasmid DNA gel retardation using two novel cyclic, phosphonate cationic lipids 2a and 2b, which were synthesized by derivatizing two diastereomeric macrocyclic phosphonates 1a and 1b with a 2-carbon hydroxylamine linker, N, N-dimethylethanolamine (3). Results: The production of cyclic phosphonate lipids 2a and 2b in 73% and 60% yields, respectively, was achieved using classical synthetic methods involving nucleophilic substitution at the phosphorus centre. Conclusions: The synthesis, aggregation and DNA binding properties of these novel cyclic phosphonate lipids suggest that they may have utility serving as gene packaging and delivery agents