Biologic Properties of Polynucleotides. Iv. Studies on the Mechanism of Complement Inhibition by Polyinosinic Acid Together with Observations on the in Vivo Effect of Polyinosinic Acid on Complement Activity.

In recent reports from this laboratory certain synthetic homioribopolyriucleotides have been found to possess anti-C' 1 activity (1, 2); of these, poly I is the most potent, as little as 0.0076 Mtmole P of this material being capable of inhibiting one C'H0,o (1). Attempts to define the mechanism of action of poly I by use of the R reagents were inconclusive, but suggested that C'1 might be most vulnerable to inactivation by poly I (1). In order to elucidate the mechanism of C' inhibition by poly I, experiments utilizing the kinetic analysis methods of Mayer and others were designed (3). The results of these experiments, with which the present report is concerned, indicate that poly I does in fact selectively inhibit C'1. In contrast to other potent C'1 inhibitors such as DFP (4) and the C'1 esterase serum inhibitor (5), poly I has no effect on C'1 esterase activity. In addition,