半乳糖衍生物阳离子脂质体基因载体的合成与性能研究有机化学专业论文.docxVIP

ABSTRACTGene ABSTRACT Gene therapy requires safe and efficient carriers to transfer DNA or siRNA to target tissues．Cationic lipids as a important type of non．viral， cationic lipids hold promise for：their reproducibility and simplicity in preparation，their non-immunogenic nature and their efficiency in forming stable complexes even with large DNA． In this work，Using galactose as starting material，two series of galactose—based cationic lipids were synthesized．The first kind of cationic lipids，with different lengths of hydrophobic chains attached to the oxygen atom of sugar ring， such as di．C 1 2．Gal．TMA， di-C 1 4一Gal-TMA，di-C 1 6一Gal-TMA，di-C 1 8一Gal-TMA，were prepared via acetylation，selective deprotection of 1-O-acetyl，trichloroacetimida- tion， glucosidation， azidation，deacetylation， 3,4一O-isopropylene protection，etherification，deprotection of isopropylidene protected， reductive amination and quatemarization．The second kind of cationic lipids，with different lengths of hydrophobic chains attached to the quatemary nitrogen atom，such as Gal-DiC 1 2MA，Gal-DiC 1 4MA， Gal-DiC 1 6MA，Gal—DiC 1 8MA were prepared via acetylation，selective deprotection of 1-0-acetyl，trichloroacetimidation，glucosidation， azidation，deacetylation，reductive amination，tertiary amination and quatemarization． The zeta potential，average particle size and poly dispersition index Ill 万方数据 of of cationic lipids and lipolexes were tested by Zetasizer Nano ZS．The results showed that the zeta potential of cationic lipids were 25—70 mV, and the zeta potential of two kinds of lipolexes were increased with the 。ncreasin2 ofot molemole ratio．whichratiowhlclq were reacneo：ached F)sitivepositive valuesValues whenwnen mole ratio at 4，2 respectively．The cationic lipids were homogeneous distribution．The average partical size of cationic lipids were 1 3 0—245 nlTl， and the lipolexes were 1 00—250 nin，except d／-C 1 8一Gal-TMA／DNA， Gal．DiCl 8MA／DNA were reached 300．450 nln at 10W mole ratio． Cationic lipids and li