P-Chiral Oligonucleotides. Effect of Configuration at Phosphorus on Transport of Tetra(thymidine Methylphosphonate)s Across Organic Liquid Membrane

Abstract

The stereodependent transport of a P-stereoregular oligonucleotide through a model organic liquid membrane is described. The electroneutral tetra(thymidine methylphosphonate) was used as oligonucleotide. The transportability increased in the order: all-RP> random distribution of P-diastereomers > all-SP. These findings extend our knowledge of the physicochemical properties of single-stranded methylphosphonate oligonucleotides in solution, and might facilitate cellular uptake of future antisense oligonucleotide drugs.