An infrared spectroscopic study of the effect of hydration on cationic lipid/DNA complexes

被引:25
作者
Choosakoonkriang, S
Wiethoff, CM
Koe, GS
Koe, JG
Anchordoquy, TJ
Middaugh, CR
机构
[1] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA
[2] Valentis Inc, Burlingame, CA 94010 USA
[3] Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA
关键词
cationic lipid; DNA; hydration; infrared spectroscopy; helper lipid;
D O I
10.1002/jps.10279
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Infrared spectroscopy was used to examine the effect of dehydration on the structure of DNA and cationic lipid/DNA complexes (CLDCs). Information regarding the effect of hydration on the interface between the cationic lipids and DNA was obtained by following subtle but reproducible changes in vibrational bands arising from the DNAbases and phosphate backbone as well as bands from the lipid ester groups within the interfacial region of the bilayer. Dehydration of supercoiled plasmid DNA induces a transition from a B-conformation in solution to a mixed conformation in the dried state. Changes in vibrations of the bases upon drying suggest a change to an A-conformation whereas vibrations from the phosphate moieties suggest A- or C-forms. Vibrational changes in the ribose ring suggest adoption of a C-conformation. When CLDCs composed of either DOTAP (1,2-dioleoyl-3-trimethylammonium-propane) or DDAB (dioctadecyldimethylammonium bromide) cationic lipids with or without equimolar amounts of the helper lipids cholesterol or DOPE (1,2-dioleoylphosphatidylethanolamin) are dried, the DNA is still able to undergo these structural transitions suggesting a nonrigid CLDC structure. The effect of dehydration on these interfacial interactions was found to be dependent on the type of cationic lipid used as well as the type of helper lipid. In addition, this work provides a simple spectroscopic analytical approach that can be used for the characterization of nonviral vectors that has potential pharmaceutical utility. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:115 / 130
页数:16
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