Distance of Hydroxyl Functionality from the Quaternized Center Influence DNA Binding and in Vitro Gene Delivery Efficacies of Cationic Lipids with Hydroxyalkyl Headgroups

In vitro gene delivery efficacies of cationic amphiphiles 1−7 (Scheme ) were measured by both the reporter gene expression assays in CHO, COS-1, HepG2, and MCF7 cells and by the whole cell histochemical X-gal staining of representative Chinese hamster ovary cells. Our results demonstrated that in vi...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2004-11, Vol.47 (23), p.5721-5728
Main Authors: Mahidhar, Yenugonda Venkata, Rajesh, Mukthavaram, Madhavendra, Sunkara Sakunthala, Chaudhuri, Arabinda
Format: Article
Language:English
Subjects:
Animals
beta-Galactosidase - biosynthesis
beta-Galactosidase - genetics
Biological and medical sciences
Biotechnology
Cations
Cell Line
Cercopithecus aethiops
Cricetinae
Cricetulus
Deoxyribonuclease I - chemistry
DNA - administration & dosage
DNA - chemistry
Fundamental and applied biological sciences. Psychology
Gene therapy
Gene Transfer Techniques
Genes, Reporter
Health. Pharmaceutical industry
Histocytochemistry
Humans
Industrial applications and implications. Economical aspects
Lipids - chemical synthesis
Lipids - chemistry
Lipids - toxicity
Microscopy, Electron, Transmission
Quaternary Ammonium Compounds - chemical synthesis
Quaternary Ammonium Compounds - chemistry
Quaternary Ammonium Compounds - toxicity
Structure-Activity Relationship
Transfection
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Summary:In vitro gene delivery efficacies of cationic amphiphiles 1−7 (Scheme ) were measured by both the reporter gene expression assays in CHO, COS-1, HepG2, and MCF7 cells and by the whole cell histochemical X-gal staining of representative Chinese hamster ovary cells. Our results demonstrated that in vitro gene delivery efficiencies of cationic lipids with hydroxyalkyl headgroups are adversely affected by increased covalent distances between the hydroxyl functionality and the cationic centers. Findings in the DNase I protection experiments and transmission electron microscopic study support the notion that such compromised gene delivery efficacies may originate from poor lipid−DNA binding interactions and significantly increased lipoplex nanosizes.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm049656j