EFFECTS OF CHEMICAL MODIFICATION ON ENZYMATIC AND TOXICOLOGICAL PROPERTIES OF PHOSPHOLIPASES A2 FROM NAJA-NAJA-NAJA AND VIPERA-RUSSELLI SNAKE-VENOMS

The effects of chemical modification with 4-NN-dimethyl amino azo benzene-4'-isothiocyanate on various biological activities of phospholipases A2, NN-XIII-PLA2 from Naja naja naja and VRV-PL-VIIIa from Vipera russelli snake venoms were investigated. Modification of the enzymes resulted in significant reduction of lethal, hemolytic, anticoagulant and enzymatic activities. The K(m) value of the modified enzymes was increased. The modified enzymes failed to induce edema in the foot pads of mice and were non-lethal up to 16 mg/kg body weight. However, considerable myotoxicity was retained, suggesting that the toxins have multiple sites for biological activities. The aggregated form obtained from modified NN-XIII-PLA2 exhibited decreased enzymatic activity and increased toxicity compared to the modified monomer. This aggregated form did not show pyrophosphatase/phosphomonoesterase activity in contrast to the aggregated form obtained from the native NN-XIII-PLA2 molecule.