Enhancing action of synthetic and natural basic polypeptides on erythrocyte-ghost phospholipid hydrolysis by phospholipase A

Abstract

The natural basic polypeptide, Gramicidin S, and the synthetic basic α-amino acid copolymers, poly-ornithine-lencine, poly-ornithine-leucine-alanine and poly-lysine-leucine, similarly to the direct lytic factor of Ringhals cobra venom, render the phospholipids in osmotic erythrocyte ghosts susceptible to the hydrolytic action of Vipera palestinae phospholipase A (phosphatide acyl-hydrolase, EC 3.1.1.4). The synthetic basic α-amino acid polymers, poly-ornithine, poly-lysine and the copolymer poly-ornithine-valine were inactive in this respect. The basicity of the polypeptides, by promoting electrostatic attraction, is held responsible for their attachment to the membrane, whereas the lipophilic side chains are invoked in the facilitation of the approach of the phospholipase to the phospholipid substrate situated inside the membrane. Gramicidin S and the synthetic basic copolymers active in facilitating the splitting of phospholipids are strongly hemolytic. The basic polyamino acids, which are inactive in enhancement of phospholipid splitting, and the Ringhals cobra direct lytic factor have little hemolytic activity.