Collect. Czech. Chem. Commun. 2001, 66, 912-922

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

Zbigniew J. Lesnikowskia,*, Marzena PrzepiĆ³rkiewicza, Yutaka Tamurab, Hideko Kajib and Eric Wickstromc

a Center of Microbiology and Virology, Polish Academy of Sciences, Lodz 93-232, Poland
b Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107, U.S.A.
c Department of Microbiology and Immunology, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, U.S.A.


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.

Keywords: Antisense oligonucleotides; Methylphosphonate analogs; Backbone modified oligonucleotides; Transport; Stereoselectivity; Liquid membrane; Cell membrane models.

References: 47 live references.