Modified oligonucleotides containing lithocholic acid in their backbones: their enhanced cellular uptake and their mimicking of hairpin structures.
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.
Kim
Su Jeong
SJ
Department of Chemistry, Division of Molecular and Life Sciences, Pohang University of Science and Technology, San 31 Hyoja Dong, Pohang 790-784, Korea.
Bang
Eun-Kyoung
EK
Kwon
Ho Jeong
HJ
Shim
Joong Sup
JS
Kim
Byeang Hyean
BH
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
D009838:Oligodeoxyribonucleotides; D008095:Lithocholic Acid