DISSOCIATION OF ENZYMATIC-ACTIVITY FROM TOXIC PROPERTIES OF THE MOST BASIC PHOSPHOLIPASE-A(2) FROM VIPERA-RUSSELLI SNAKE-VENOM BY GUANIDINATION OF LYSINE RESIDUES

The most basic phospholipase A(2) VRV-PL-VIIIa purified from Russell's viper venom is a toxic enzyme. It induced neurotoxicity, myotoxicity, and oedema and was lethal to mice at 5.3 mu g/g body weight. It also inhibited the coagulation of the human plasma. The epsilon-amino groups of lysine residues of the toxic enzyme VRV-PL-VIIIa were guanidinated with o-methylisourea. Guanidination of the enzyme did not alter the enzymatic activity markedly. The guanidinated enzyme became non-lethal in doses up to 16 mu g/g body weight, and failed to elicit neurotoxic symptoms in experimental animals and oedema in the foot pads of mice. Also, its myotoxic and anticoagulant potencies were decreased significantly.