title: Modified oligonucleotides containing lithocholic acid in their backbones: their enhanced cellular uptake and their mimicking of hairpin structures.
abstract: Their enhanced cell permeability and their ability to mimic DNA structures make modified oligodeoxyribonucleotides (ODNs) very important substances for increasing our understanding of cell biology and for therapeutic applications. Lithocholic acid is a hydrophobic secondary bile acid that is a substrate of nuclear Pregnane X receptor (PXR). We designed and synthesized novel lithocholic acid-based ODNs (L-ODNs) by using a new phosphoramidite derived from lithocholic acid. By comparing data obtained from circular-dichroism, melting-point, and theoretical studies, we believe that these L-ODNs adopt DNA hairpin structures. Furthermore, L-ODNs have enhanced cellular uptake properties with respect to regular ODNs. To demonstrate their enhanced cell permeabilities, we carried out cellular uptake experiments of L-ODNs in HeLa cells. By attaching fluorescein as a fluorescence label and using confocal microscopy, we observed that the permeability of L-ODNs is much higher than that of natural ODNs.
authors.affiliation: Department of Chemistry, Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31 Hyoja Dong, Pohang 790-784, Korea.
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Bang
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Joong Sup
authors.initials: JS
authors.lastname: Shim
authors.forename: Byeang Hyean
authors.initials: BH
authors.lastname: Kim
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability; D002942:Circular Dichroism; D006367:HeLa Cells; D006801:Humans; D008095:Lithocholic Acid / Q000737:chemistry*; D008956:Models, Chemical; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D013696:Temperature
chemical_list: D009838:Oligodeoxyribonucleotides; D008095:Lithocholic Acid