title: Synthesis and cellular activity of stereochemically-pure 2'-O-(2-methoxyethyl)-phosphorothioate oligonucleotides.
abstract: Stereochemically-pure 2'-O-(2-methoxyethyl)-phosphorothioate (PS-MOE) oligonucleotides were synthesized from new chiral oxazaphospholidine-containing nucleosides. Thermal stability studies showed that the incorporation of Rp-PS linkages increased RNA-binding affinity. In cells, a full Rp-PS-MOE splice-switching oligonucleotide targeting part of the ferrochelatase gene was more potent than its Sp-PS counterpart, but of similar potency to the stereorandom PS-parent sequence.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
authors.forename: H L
authors.initials: HL
authors.lastname: Lightfoot
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
authors.forename: F
authors.identifier: 0000-0003-2973-5820
authors.initials: F
authors.lastname: Halloy
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
authors.forename: A L
authors.initials: AL
authors.lastname: Malinowska
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
authors.forename: C
authors.initials: C
authors.lastname: Berk
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
authors.forename: A
authors.initials: A
authors.lastname: Behera
authors.affiliation: Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.
authors.forename: D
authors.identifier: 0000-0002-9644-134X
authors.initials: D
authors.lastname: Schümperli
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. jonathan.hall@pharma.ethz.ch.
authors.forename: J
authors.identifier: 0000-0003-4160-7135
authors.initials: J
authors.lastname: Hall
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D005294:Ferrochelatase / Q000235:genetics; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D054735:Phosphorothioate Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D013237:Stereoisomerism
chemical_list: D001055:Apolipoproteins B; D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; D012333:RNA, Messenger; D005294:Ferrochelatase