الفهرس 
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Abstract
After a focused review about polyamines, their classification, polyamine conjugates and their different biological uses also chemistry and biochemistry of non-viral gene therapy and siRNA delivery, synthetic chemistry studies are described for the preparation of novel lipopolyamines for DNA and siRNA delivery. A series of conjugates in which the tetra-amine spermine (1,12-diamino-4,9-diazadodecane, the cationic moiety) and the two fatty acid chains (lipophilic moiety ) are linked by amide bonds at the secondary amino groups to form N4,N9 -diacyl spermine were designed and synthesized. To investigate a potentially less toxic and more efficient vector, unsymmetrical N-diacyl spermines, saturated and unsaturated N4,N9 lipopolyamines were synthesized.
Also, some spermine conjugates with one aliphatic chain and one steroid were synthesized. These incorporate Cholesteryl carbamates amide of spermine. Also we were investigating N-heterocyclic cationic head groups (e.g. imidazole, pyridine, and quinoline) aiming for a final amine pKa of around 6.5 (5-7) to assist in swelling via the proton sponge effect. Here the import of protons with water molecules, and possibly with chloride counter ions, leads to swelling and eventual rupture of the sub-cellular organelle, the endosome, thus helping to avoid lysosomal degradation and leading to more efficient transfection. As we control the functional groups in and around the N-heterocycles, we can make them more (or less) basic. We predict that this control of the pKa will be important in facilitating endosome escape.
Aiming to have spermine conjugates specific for siRNA delivery Michael addition was chosen to conjugate spermine with two unsymmetrical fatty chains via 3 carbons linker.