Synthesis and cellular activity of stereochemically-pure 2'-O-(2-methoxyethyl)-phosphorothioate oligonucleotides

  • Chem Commun (Camb). 2017 Jan 3;53(3):541-544. doi: 10.1039/c6cc08473g.
M Li  1 ,  H L Lightfoot  1 ,  F Halloy  1 ,  A L Malinowska  1 ,  C Berk  1 ,  A Behera  1 ,  D Schümperli  2 ,  J Hall  1
Affiliations
  • 1. Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zürich, 8093 Zürich, Switzerland. [email protected].
  • 2. Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.
PMID: 27966701 DOI: 10.1039/c6cc08473g
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.

Products