P-chiral oligonucleotides. Effect of configuration at phosphorus on transport of tetra(thymidine methylphosphonate)s across organic liquid membrane

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