Propynylated phosphodiester oligonucleotides inhibit ICAM-1 expression in A549 cells on electroporation.
Oligodeoxynucleotides (ODN) are used largely as either primers, antisense, or triplex-forming units. Phosphodiester ODN (PO-ODN), which are very rapidly degraded by exonucleases, must be protected at their ends. Even so, their life span inside cells is quite short. Phosphorothioate ODN (PS-ODN) are less sensitive to nucleases and are extensively used as antisense. Unfortunately, unlike PO-ODN, they interact with a number of molecules, including proteins, in addition to their specific nucleic acid targets. Their affinity for their target is lower than that of PO-ODN. PS-ODN containing propyne groups on C5 of pyrimidine have been shown to have a higher affinity toward their nucleic acid target. Here, we show that propynylated PO-ODN are more stable and much more efficient than their propyne-free counterparts. They are not efficient when they are used as lipoplexes, but they act as specific antisense on electroporation.
Meunier
L
L
Glycobiologie, Vectorologie et Trafic Intracellulaire, Centre de Biophysique Moléculaire, CNRS, Orléans, France.
Monsigny
M
M
Roche
A C
AC
D000480:Alkynes / Q000737:chemistry*; D004355:Drug Stability; D018274:Electroporation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008081:Liposomes; D008845:Microinjections; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000480:Alkynes; D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense; C022030:methylacetylene; D018799:Intercellular Adhesion Molecule-1