Phosphorothioate (p=s) oligonucleotides containing modified nucleotides with six-membered azasugars and use for aids therapy thereof

摘要

PURPOSE: Provided are phosphorothioate oligonucleotides containing modified nucleotides with six-membered azasugars and their use for AIDS therapy. The phosphorothioate oligonucleotides block HIV attachment, show broad spectrum of anti HIV activity to various HIV mutants and have low toxicity. CONSTITUTION: The phosphorothioate oligonucleotide is represented by the formula(1) in which five-membered ribose is substituted with six-membered azasugar. In the formula, n is an integer of 0-30; B is a natural nucleotide base or a modified nucleotide base with or without a protection group; X is hydrogen, a hydroxyl protection group, a conjugate group or an oligonucleotide; and Y is hydrogen, phosphate, activated phosphate, activated phosphite or a solid support, a conjugate group, an oligonucleotide. The pharmaceutical composition for the AIDS therapy contains the above phosphorothioate oligonucleotide as an active ingredient.