Chimeric DNA/RNA ribozymes containing propanediol

摘要

DNA-RNA-(Pr)n-RNA-DNA ribozymes of formula III or IV:in whichX and Z comprise DNA sequences that base pair with an RNA substrate at positions adjacent to an RNA cleavage site;cugaugag and cgaaa are catalytic RNA sequences;Pr is a spacer residue -P(O)(OH)-O-CH2CH2CH2-O-; andR is a bridging residue -O-CH2-C(CH2OH)(CH3)-CH2-O-.The ribozymes can be made on any DNA synthesizer using phosphoramidite chemistry, and are useful as therapeutic agents for treating viral or endogenous RNA-mediated diseases. Preferred ribozymes target a sequence in the U5 region of HIV-1.