Chemical ribonucleases. 2. Design and hydrolytic activity of the ribonuclease mimics on the basis of diazabicyclo[2.2.2]octane with a differing number of positive charges

A procedure was proposed allowing one to synthesize RNA mimics on the basis of conjugates of diazabicyclo[2.2.2]octane with imidazole bearing a varyin g number of positive charges (nDm series, where n is the number of positive charges at neutral pH, m is the code of an imidazole-containing fragment o f the catalytyc domain: 1, histamine; 2, histidine methyl ester). The hydro lytic activity of six compounds of this series was studied under physiologi cal conditions using in vitro transcript of human mitochondrial tRNA(Lys) a s a substrate. It was shown that the rate of RNA hydrolysis with nDm conjug ates rises with an increase in the number of positive charges: an approxima tely 30-fold acceleration of hydrolysis was observed with an increase in th e total charge of the consruct from +2 to +4.