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- W2001569140 abstract "Inspired by the previously reported superior gene transfer efficacies of amine headgroup-containing cationic lipids to their hydroxy counterparts, in the present structure−activity investigation we have compared the relative in vitro gene transfer efficacies of eight newly synthesized structural analogues of our previously reported lipids 1−4, namely the four 3,4-diaminopyrrolidinium chloride structural analogues (lipids 9−12, Chart 1) and the N-BOC-protected precursors of these amine analogues (lipids 5−8, Chart 1) with our previously reported lipids 1−4 (Chart 1) in five cultured cell lines. In contrast to the above-mentioned earlier reports, except for the superior or comparable transfection efficacies of the diaminopyrrolidinium lipids with distearyl and stearyloleyl chains (lipid 11 and 12 respectively, Chart 1) in MCF-7 and HEK293T cells, the relative transfection efficacies of the other diamino analogues were found to be much lower than their dihydroxy counterparts. The results of the DNase I sensitivity assays indicate that enhanced degradation of DNA associated with lipids 9−12 by cellular DNase I might play an important role behind their seriously compromised transfection efficacies. In addition, the present structure−activity investigation revealed a strikingly cell tropic transfection behavior of lipid 6 (Chart 1). While lipids 5, 7, and 8 were found to be either poor or essentially incompetent in transfecting all the five cells, lipid 6 was remarkably efficacious in transfecting kidney cells (COS-1 and HEK293T cells) at lipid:DNA charge ratios 3:1 and 1:1 when used in combination with equimolar amounts of DOPE and DOPC." @default.
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- W2001569140 date "2005-04-30" @default.
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- W2001569140 title "In Vitro Gene Transfer Efficacies of <i>N</i>,<i>N</i>-Dialkylpyrrolidinium Chlorides: A Structure−Activity Investigation" @default.
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- W2001569140 doi "https://doi.org/10.1021/jm050128x" @default.
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