RNA-cleaving agents

Sequence-selective RNA scission was accomplished by the attachment of oligo-amines to synthetic DNA oligomers [18]. The cleaving agent 16, composed of di-ethylenetriamine (DETA) linked to 19-mer DNA, hydrolyzed linear 30-mer RNA strand 17 in a sequence-selective manner (Scheme 13.4). Hence, treatment of the linear RNA in the presence of DNA-DETA complex 16 and EDTA at pH 8 for 4 h at 50 °C, furnished, with good selectivity, the scission products 18 and 19, albeit with a low conversion (10%) of the starting material. 

Antigene sequences and ribozymes form two additional classes of antisense agents. However, the therapeutic potential of these agents is only now beginning to be appraised. Certain RNA sequences can function as catalysts. These so-called ribozymes function to catalyse cleavage at specific sequences in a specific mRNA substrate. Many ribozymes will cleave their target mRNA where there exists a particular triplet nucleotide sequence G-U-C. Statistically, it is likely that this triplet will occur at least once in most mRNAs. 

Proteases also are involved in viral maturation. For example, in picomavirus replication the virus RNA is translated into large virus precursor polypeptides. These then are cleaved by a viral protease(s) into the viral proteins (26,27). This opens the possibility that specific inhibitors for the viral processing protease could be used as antiviral agents. 

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